Title:Urokinase Type Plasminogen Activator and the Molecular Mechanisms of its Regulation in Cancer. VOLUME: 24 ISSUE: 10. Author(s):Juan F. Santibanez*. Affiliation:Group for Molecular Oncology, Institute for Medical Research (IMI), University of Belgrade, Dr. Subotica 4, 11129 Belgrade. Keywords:uPA, urokinase type plasminogen activator, uPAR, urokinase type plasminogen activator receptor, cancer, signaling, epigenetic, microRNA, therapies.. Abstract:Background: Urokinase type plasminogen activator (uPA) is a 53-kDa serine protease initially synthesized as a catalytically inactive single chain polypeptide. Inactive-uPA is subject to proteolytic cleavage, which results in the two-chain active protein. uPA plays key roles in the enhancement of cell malignancy during tumor progression. Objectives: The main objective of this review was to analyze and describe the main molecular mechanisms involved in the regulation of uPA expression in cancer Methods: Searching literature to evaluate and define ...
Data accumulated over the latest two decades have established that the serine protease urokinase-type plasminogen activator (uPA) is a potential therapeutic target in cancer. When designing inhibitors of the proteolytic activity of serine proteases, obtaining sufficient specificity is problematic, because the topology of the proteases active sites are highly similar. In an effort to generate highly specific uPA inhibitors with new inhibitory modalities, we isolated uPA-binding RNA aptamers by screening a library of 35 nucleotides long 2′-fluoro-pyrimidine RNA molecules using a version of human pro-uPA lacking the epidermal growth factor-like and kringle domains as bait. One pro-uPA-binding aptamer sequence, referred to as upanap-126, proved to be highly specific for human uPA. Upanap-126 delayed the proteolytic conversion of human pro-uPA to active uPA, but did not inhibit plasminogen activation catalyzed by two-chain uPA. The aptamer also inhibited the binding of pro-uPA to uPAR and the ...
The urokinase-type plasminogen activator (u-PA)/plasmin system plays an important role in promoting cell migration and invasion, an effect which is largely ascribed to the proteolytic activity of these enzymes. We investigated whether u-PA modulates integrin-dependent T lymphocyte migration and adhesion on fibronectin independently of its plasminogen activator function. Here we report that u-PA reduced the spontaneous and phorbol 12-myristate 13-acetate-induced migration of peripheral blood T lymphocytes on fibronectin by 20-50%, decreased the T lymphocyte and alpha4beta1(+)/alpha5beta1(+) K562 cell adhesion on fibronectin by 30-40%, and completely suppressed integrin alpha4beta1-dependent T lymphocyte and alpha4beta1(+)/alpha5beta1(+) K562 cell adhesion to the LDV-containing 40-kDa fibronectin fragment. The u-PA receptor was not essential for this effect. In contrast, adhesion of alpha4beta1(-)/alpha5beta1(+) K562 cells to an RGD-containing fibronectin fragment was unaffected. A recom
Our previous study showed that proMMP-9 was activated by MMP-3 directly, and that proMMP-3 was activated by plasmin. It was postulated that the proMMP-9 activation mechanism through the protease-protease cascade existed even in vivo. The purpose of the present study was to clarify the clinical significance of the combined expression of MMP-9, MMP-3, and urokinase-type plasminogen activator (uPA) in colorectal cancer, and the role of MMP-3 or uPA expression as an activator for MMP-9. The expression of both MMP-9 and uPA was found to be correlated with liver metastasis, and with survival rate. The coexpression of MMP-9 and uPA by tumor cells was also significantly correlated with postoperative hepatic recurrence and survival rate. MMP-9 tended to be coexpressed with uPA, and was consistently associated with MMP-3 localized at the tumor-invasive front with inflammatory cells such as monocyte-macrophages. In gelatin zymography, the MMP-9 active form tended to be identified in the tumors that coexpressed
Internalization of the urokinase-type plasminogen activator (uPA) requires two receptors, the uPA receptor (uPAR) and the low density lipoprotein receptor-related protein (LRP)/alpha2-macroglobulin (alpha2M) receptor. Here, we address whether protein kinases are involved in the internalization of uPA by human melanoma cells. Initially, we found that the internalization of uPA was significantly inhibited by the serine/threonine protein kinase inhibitors staurosporine, K-252a and H-89, but not by the tyrosine kinase inhibitors, genistein and lavendustin A. Internalization of uPA was also inhibited by a pseudosubstrate peptide for cAMP-dependent protein kinase (PKA), but not by a pseudosubstrate peptide for protein kinase C. We confirmed a requirement for PKA-activity and implicated a specific isoform by using an antisense oligonucleotide against the regulatory subunit RI alpha of PKA which suppresses PKA-I activity. Exposure of cells to this oligonucleotide led to a specific, dose-dependent ...
Fingerprint Dive into the research topics of Down-regulation of secreted lymphocyte antigen-6/urokinase-type plasminogen activator receptor-related peptide-1 (SLURP-1), an endogenous allosteric α7 nicotinic acetylcholine receptor modulator, in murine and human asthmatic conditions. Together they form a unique fingerprint. ...
Urokinase-type plasminogen activator expression is induced in the mouse mammary gland during development and post-lactational involution. We now show that primiparous plasminogen-deficient (Plg(−/−)) mice have seriously compromised mammary gland development and involution. All mammary glands were underdeveloped and one-quarter of the mice failed to lactate. Although the glands from lactating Plg(−/−) mice were initially smaller, they failed to involute after weaning, and in most cases they failed to support a second litter. Alveolar regression was markedly reduced and a fibrotic stroma accumulated in Plg(−/−) mice. Nevertheless, urokinase and matrix metalloproteinases (MMPs) were upregulated normally in involuting glands of Plg(−/−) mice, and fibrin did not accumulate in the glands. Heterozygous Plg(+/−) mice exhibited haploinsufficiency, with a definite, but less severe mammary phenotype. These data demonstrate a critical, dose-dependent requirement for Plg in lactational ...
Isolation and characterization of an inhibitory human monoclonal antibody specific to the urokinase-type plasminogen activator, ...
BioAssay record AID 215978 submitted by ChEMBL: Compound was tested for microPa) Urokinase-type plasminogen activator from human urine.
Background: Moderate alcohol consumption has been correlated to reduced coronary artery disease (CAD) risk and mortality. This alcohol effect may be mediated in part by an increased endothelial cell (EC) fibrinolysis. ECs synthesize fibrinolytic proteins, tissue plasminogen activator (t-PA), urokinase type plasminogen activator (u-PA), and plasminogen activator inhibitor type-1(PAI-1). In addition, they synthesize and regulate receptors for fibrinolytic proteins, namely (t-PA and plasminogen receptor) Annexin II and u-PA receptor (u-PAR). These receptors play an important role in the regulated expression of receptorbound plasminogen activator conversion of receptor-bound plasminogen to receptor-bound plasmin on the EC surface (surface-localized fibrinolytic activity). Therefore, systemic factors, such as ethanol, that affect the level, or activity or interaction of one or more of these components, resulting in the increased expression of surface-localized EC fibrinolytic activity, will be ...
An elevated level of EMMPRIN in cancer tissues have been correlated with tumor invasion in numerous cancers including oral cavity and larynx. Although EMMPRINs effect has been generally attributed to its MMP inducing activity, we have previously demonstrated in breast cancer model that EMMPRIN can also enhance invasion by upregulating uPA. In this study, the role of EMMPRIN in regulating uPA and invasion was investigated in oral squamous cell carcinoma (OSCC) progression. Precancerous and invasive oral tumoral tissues were used as well as the corresponding cell lines, DOK and SCC-9 respectively. The paracrine regulation of uPA by EMMPRIN was investigated by treating culture cells with EMMPRIN-enriched membrane vesicles. UPA expression was analyzed by qPCR and immunostaining and the consequence on the invasion capacity was studied using modified Boyden chamber assay, in the presence or absence of EMMPRIN blocking antibody, the uPA inhibitor amiloride or the MMP inhibitor marimastat. OSCC tumors were
Urokinase, also known as urokinase-type plasminogen activator (uPA), is a serine protease present in humans and other animals. The human urokinase protein was discovered, but not named, by McFarlane and Pilling in 1947. Urokinase was originally isolated from human urine, and it is also present in the blood and in the extracellular matrix of many tissues. The primary physiological substrate of this enzyme is plasminogen, which is an inactive form (zymogen) of the serine protease plasmin. Activation of plasmin triggers a proteolytic cascade that, depending on the physiological environment, participates in thrombolysis or extracellular matrix degradation. This cascade had been involved in vascular diseases and cancer progression. Urokinase is encoded in humans by the PLAU gene, which stands for plasminogen activator, urokinase. The same symbol represents the gene in other animal species ...
PubMedID: 23242529 | Adrenomedullin enhances invasion of human extravillous cytotrophoblast-derived cell lines by regulation of urokinase plasminogen activator expression and s-nitrosylation. | Biology of reproduction | 2/1/2013
Regulation of the extracellular matrix (ECM) plays an important functional role either in physiological or pathological conditions. The plasminogen activation (PA) system, comprising the uPA and tPA proteases and their inhibitor PAI-1, is one of the main suppliers of extracellular proteolytic activity contributing to tissue remodeling. Although its function in development is well documented, its precise role in mouse embryonic stem cell (ESC) differentiation in vitro is unknown. We found that the PA system components are expressed at very low levels in undifferentiated ESCs and that upon differentiation uPA activity is detected mainly transiently, whereas tPA activity and PAI-1 protein are maximum in well differentiated cells. Adipocyte formation by ESCs is inhibited by amiloride treatment, a specific uPA inhibitor. Likewise, ESCs expressing ectopic PAI-1 under the control of an inducible expression system display reduced adipogenic capacities after induction of the gene. Furthermore, the adipogenic
Urokinase, also known as urokinase-type plasminogen activator (uPA), is a serine protease present in humans and other animals. The human urokinase protein was discovered, but not named, by McFarlane and Pilling in 1947. Urokinase was originally isolated from human urine, and it is also present in the blood and in the extracellular matrix of many tissues. The primary physiological substrate of this enzyme is plasminogen, which is an inactive form (zymogen) of the serine protease plasmin. Activation of plasmin triggers a proteolytic cascade that, depending on the physiological environment, participates in thrombolysis or extracellular matrix degradation. This cascade had been involved in vascular diseases and cancer progression. Urokinase is encoded in humans by the PLAU gene, which stands for plasminogen activator, urokinase. The same symbol represents the gene in other animal species. The PLAU gene encodes a serine protease (EC 3.4.21.73) involved in degradation of the extracellular matrix and ...
Linkage studies indicate that the same region of chromosome 10 contains a risk locus for late onset Alzheimer disease (LOAD) and a QTL for plasma Aβ42 levels suggesting that a single locus may influence risk for AD by elevating plasma Aβ42 [Ertekin-Taner et al., 2000; Myers et al., 2000]. A strong positional and biological candidate is the urokinase-plasminogen activator (PLAU) gene. Eight polymorphisms spanning the entire gene were examined using case control (CC) and family-based association methods. No association was observed by any method making it unlikely that variation in PLAU explains our linkage data. © 2003 Wiley-Liss, Inc.
Advertisement] MAGNUM(Q-switched Nd:YAG Laser) - Manufacturer: (www.i-dana.com)]. - Cell migration. Cells move by rolling as well as by sliding and crawling, presumably with the help of actomyosin, polymerized actin and actin gel without myosin. The epithelial barrier, which is a group of epithelial cells, inhibit cell migration when it is adjacent to the surrounding cells, and epithelial cells build up when cells are in contact with each other. Cells cannot pass through the fibrin clot without melting the fibrin barrier. In this process, plasminogen activation system, composed of tissue plasminogen activator (tPA) and urokinase plasminogen activator (uPA), which act as enzymatic proteases, converts plasminogen to plasmin, a substance capable of degrading fibrin. These activators and their receptors are known to be upregulated in keratinocyte.. Plasminogen activator inhibitor (PAI), which inhibits and controls the plasminogen activator system, prevents chronic non-healing wound from excessive ...
Glomerular mesangial cells (MCs) are central to the pathogenesis of progressive glomeruli-associated renal diseases. However, molecular mechanisms underlying changes in MC functions still remain poorly understood. Here, we show that in MCs, the urokinase-type plasminogen activator (uPA) induces, via its specific receptor (uPAR, CD87), upregulated expression of the complement anaphylatoxin C5a receptor (C5aR, CD88), and modulates C5a-dependent functional responses. This effect is mediated via the interaction of the uPA-specific receptor (uPAR, CD87) and gp130, a signal transducing subunit of the receptor complexes for the IL-6 cytokine family. The Janus kinase Tyk2 and the transcription factor Stat3 serve as downstream components in the signaling cascade resulting in upregulation of C5aR expression. In vivo, expression of C5aR and uPAR was increased in the mesangium of wild-type mice in a lipopolysaccharide (LPS)-induced model of inflammation, whereas in uPAR -/- animals C5aR expression remained ...
5615 The upregulated expression of the urokinase type plasminogen activator (uPA)-system is associated with invasion, neo-angiogenesis and metastatic spread of tumors and strongly correlates with poor prognosis of breast and other cancer patients. Therefore, inhibition of the uPA-system is considered a promising approach for anti-cancer and/or anti-metastatic therapy of cancer patients. WX-340 a highly specific and selective inhibitor of uPA was evaluated for its in-vivo activity in a rat and a mouse animal model.. The compound was shown to inhibit human uPA with a Ki of 0.012 µM, rat uPA with 0.017 µM and mouse uPA with 0.170 µM while the inhibition constants for other serine proteases such as (human) plasmin, thrombin, tissue-PA and factor Xa were ,190 µM.. The anti-tumor and anti-metastatic activities of WX-340 were evaluated in a rat tumor model (Brown Norwegian rats, n=18 per group) bearing orthotopically inoculated and spontaneously metastasising BN-472 mammary carcinoma. The animals ...
The urokinase type plasminogen activator (uPAR) is a three domain GPI-anchored cell surface receptor. uPAR expression is strongly up-regulated and represents a negative prognostic factor in various tumors, including hematologic malignancies. uPAR expression is post-transcriptionally regulated by RNA binding proteins (RBPs). RBPs bind specific sequences in the 3untranslated region (3UTR) of uPAR-mRNA, stabilizing or destabilizing the transcript. The 3UTR of transcripts from a large number of genes includes target sequences also for small translational repressors RNAs (miRNAs). miRNAs play key roles in many cellular pathways; their aberrant expression is a common feature of various malignancies. We selected three miRNAs miR-146a, miR-335 and miR-622 that could bind the 3UTR of uPAR-mRNA; these three miRNAs, as reported in literature, are expressed in CD34+ HSC or in acute myeloid leukemia (AML) cells and can act as oncosuppressors by inhibiting oncogene expression. We found that selected ...
Glucose regulated protein 78 promotes cell invasion via regulation of uPA production and secretion in colon cancer cells;kpubs;kpubs.org
ER3 and PR are important regulators of growth and differentiation in the mammary gland and the female reproductive tract. Both are also involved in the development of malignant tumors ,(1) . pS2 is an estrogen-inducible protein, the function of which is still unknown. However, it is assumed that pS2 is associated with tissue differentiation (2) . Urokinase-type plasminogen activator catalyzes the conversion of inactive plasminogen to active plasmin, which contributes to the degradation of basement membranes in tumor invasion and metastasis (3) . PAI-1 inhibits the activity of urokinase-type plasminogen activator by forming an enzyme-inhibitor complex (4) .. ER, PR, pS2, and PAI-1 have been reported to be prognostic as well as predictive parameters in primary breast cancer patients. Negative correlations of ER and PR protein levels to tumor size, number of axillary lymph nodes, and histological grade have been reported frequently (5, 6, 7, 8) . ER and PR are also important predictors of longer ...
The Acid Fast Bacteria (AFB) Stain Kit is intended for use in the histological visualization of Acid Fast Bacteria and Tubercle Bacilli. This kit…https://lnkd.in/eFnwEaH https://lnkd.in/e- ...
Supplementary Materialspathogens-09-00132-s001. Navitoclax irreversible inhibition chromatin, the enrichment of acetylated lysine 9 in histone 3 (H3K9ac) was looked into using the TLR-focused ChIP array system. The data showed that illness with WT gonococci led to higher H3K9ac enrichment in the promoters of pro-inflammatory mediators genes, many TLRs, adaptor proteins and transcription factors, suggesting gene activation when compared to infection with the Gc-HDAC-deficient mutant. Taken together, the data suggest that gonococci can exert epigenetic modifications on sponsor cells to modulate particular macrophage defense genes, leading to a maladaptive state of qualified immunity. is definitely a strict human being pathogen that causes the sexually transmitted illness termed gonorrhea. Importantly, gonorrhea is definitely a major worldwide public health problem given its estimated yearly incidence of 87 million infections [1]. In addition to causing a high incidence of illness and disease, the ...
Disruption of E3 ubiquitin ligase activity in immature zebrafish mutants prospects AZD8330 to failing in Notch signaling excessive amounts of neurons and depletion of neural progenitor cells. discharges reported in immature zebrafish subjected to convulsant medications. Electrophysiological recordings from agar immobilized mutants at three times postfertilization (dpf) verified the incident of electrographic seizure activity; seizure-like behaviors had been observed during locomotion video tracking of freely behaving mutants also. To recognize genes differentially portrayed in the mutant and offer understanding into molecular pathways that may mediate these epileptic phenotypes a transcriptome evaluation was performed using microarray. Interesting applicant genes were additional AZD8330 analyzed using typical reverse transcriptasepolymerase string response (RT-PCR) and real-time quantitative PCR (qPCR) aswell as whole-mount hybridization. Around 150 genes some implicated in advancement ...
Important modulators of the activity of plasminogen activators. The inhibitors belong to the serpin family of proteins and inhibit both the tissue-type and urokinase-type plasminogen activators ...
An extensive structural manifold of short hydrogen bond-mediated, active site-directed, serine protease inhibition motifs is revealed in a set of over 300 crystal structures involving a large suite of small molecule inhibitors (2-(2-phenol)-indoles and 2-(2-phenol)-benzimidazoles) determined over a wide range of pH (3.5-11.4). The active site hydrogen-bonding mode was found to vary markedly with pH, with the steric and electronic properties of the inhibitor, and with the type of protease (trypsin, thrombin or urokinase type plasminogen activator (uPA)). The pH dependence of the active site hydrogen-bonding motif is often intricate, constituting a distinct fingerprint of each complex. Isosteric replacements or minor substitutions within the inhibitor that modulate the pK(a) of the phenol hydroxyl involved in short hydrogen bonding, or that affect steric interactions distal to the active site, can significantly shift the pH-dependent structural profile characteristic of the parent scaffold, or ...
An extensive structural manifold of short hydrogen bond-mediated, active site-directed, serine protease inhibition motifs is revealed in a set of over 300 crystal structures involving a large suite of small molecule inhibitors (2-(2-phenol)-indoles and 2-(2-phenol)-benzimidazoles) determined over a wide range of pH (3.5-11.4). The active site hydrogen-bonding mode was found to vary markedly with pH, with the steric and electronic properties of the inhibitor, and with the type of protease (trypsin, thrombin or urokinase type plasminogen activator (uPA)). The pH dependence of the active site hydrogen-bonding motif is often intricate, constituting a distinct fingerprint of each complex. Isosteric replacements or minor substitutions within the inhibitor that modulate the pK(a) of the phenol hydroxyl involved in short hydrogen bonding, or that affect steric interactions distal to the active site, can significantly shift the pH-dependent structural profile characteristic of the parent scaffold, or ...
Urokinase type Plasminogen Activator Human Chromogenic Activity Assay Kit (ab108915). Sensitivity | 6 mU/mL. Detect uPA in biological fluids in 1 hr.
Structural alterations within microvessels also occur within hours after the onset of focal ischemia. Hamann et al24 demonstrated a significant reduction in the matrix protein constituents of the basal lamina across all microvessel diameters. Simultaneously, pro-matrix metalloproteinase (MMP)-2, whose active form is known to degrade collagen and laminin, is generated and released immediately after ischemia onset, as demonstrated by high-quality biochemical techniques.25 Tissue expression of this protease in the nonhuman primate is directly related to the number of neurons injured within the 7-day timeframe of the experiment and to the size of tissue injury.25,26 Other proteases generated simultaneously, including urokinase plasminogen activator from the endothelium, are not related to neuron injury. Pro-MMP-2 and urokinase plasminogen activator are associated with both microvessels and neurons.26 In addition, the activation apparatus for pro-MMP-2, including MT1-MMP and MT3-MMP, as well as ...
The clinical relevance of invasion factors urokinase-type plasminogen activator (uPA)/PAI-1 and HER-2 status was evaluated in lymph node-negative breast cancer patients (N = 118) without adjuvant systemic therapy after long-term follow-up of more than 10 years (median, 126 months). Levels of uPA and its inhibitor PAI-1 were prospectively measured by enzyme-linked immunosorbent assay (ELISA) in primary tumor tissue extracts. HER-2 gene amplification (HER-2 AMP) was evaluated by fluorescence in situ hybridization (FISH), and HER-2 protein overexpression (HER-2 EXP) was evaluated by immunohistochemistry (IHC) on parallel-cut formalin-fixed paraffin-embedded tissue sections. uPA/PAI-1 was high (either one or both factors were high) in 44% of the tumors. HER-2 AMP was detected by FISH in 33% of the patients, and HER-2 EXP was found by IHC in 44% of the patients. In a multivariate analysis of established and tumor-biologic prognostic factors, uPA/PAI-1 was the only independent prognostic factor for ...
Stromal macrophages of different phenotypes can contribute to the expression of proteins that affects metastasis such as urokinase-type plasminogen activator (uPA), its receptor uPAR, and plasminogen activator inhibitor-1 (PAI-1), but knowledge of how essential their contribution is in comparison to the cancer cells in small cell lung cancer (SCLC) and lung squamous cell carcinoma (SCC) is lacking. The expression of uPA, uPAR, and PAI-1 and of the matrix metalloproteinases (MMP)-2 and MMP-9 were studied in human macrophages of M1 and M2 phenotype and compared to a lung SCC (NCI-H520) and a SCLC (NCI-H69) cell line. Effects of treatment with conditioned media (CM) from M1 and M2 macrophages on the expression of these genes in H520 and H69 cells as well as effects on the cell growth were investigated. In addition, data on the stromal macrophages immunoreactivity of uPAR, MMP-2, and MMP-9 in a few SCC and SCLC biopsies was included. uPAR, MMP-2, and MMP-9 were confirmed in stromal cells including ...
Mouse Monoclonal Anti-u-Plasminogen Activator/Urokinase Antibody (B032M). Validated: ELISA. Tested Reactivity: Rat. 100% Guaranteed.
HGF, a cytokine produced in a tumor microenvironment, may affect various aspects of the invasive phenotype of carcinoma cells (31, 34, 35). We observed that HGF increased the CXCR4 promoter activity as well as the mRNA and protein levels in estrogen-responsive MCF-7 breast carcinoma cells. On the contrary, in MDA-MB231 highly invasive, estrogen-resistant breast carcinoma cells, HGF reduced CXCR4 transactivation, decreasing mRNA and protein levels.. The progression of mammary adenocarcinomas has been associated with deregulation of several signaling molecules and epigenetic mechanisms (36, 37). As shown for urokinase-type plasminogen activator, a member of plasminogen activation system important for tumor invasiveness (26), DNA methylation blockade seemed to induce CXCR4 in MCF-7 cells, increasing the mRNA level to reach the elevated value of MDA-MB231 cells. Because methylation did not seem to influence CXCR4 transcription by HGF, the molecular basis of the opposite CXCR4 expression responses to ...
The tissue-specific distribution of tissue-type and urokinase-type plasminogen activator (t-PA and u-PA) and their inhibitor type 1 (PAI-1) was analyzed at mRNA level in five major rat organ tissues. t-PA mRNA was detected in lung, kidney, heart, and liver. u-PA mRNA was detected in kidney and lung. Presence of PA mRNA correlated with the ...
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Description: PAI-2 is an inhibitory serpin expressed mainly in keratinocytes, activated monocytes, and placental trophoblasts. It exists predominantly as a 47 kDa nonglycosylated intracellular protein which can be induced to be secreted as 60 kDa glycoprotein. The glycosylated and unglycosylated forms of PAI-2 are equally effective as inhibitors of urokinase-type plasminogen activator (uPA), the only established physiological target of this serpin. PAI-2 has a unique ability to form dormant polymers spontaneously and reversibly under physiological conditions. The physiological relevance of this property, which is neither a consequence of any mutation in the PAI-2 gene nor associated with any known disorder, is still unclear. However, it appears that the formation of intracellular dormant polymers may be important for the controlled release of the inhibitor from PAI-2 producing cells. Plasma levels of PAI-2 are usually low or undetectable, except during pregnancy and in some forms of monocytic ...
Description: PAI-2 is an inhibitory serpin expressed mainly in keratinocytes, activated monocytes, and placental trophoblasts. It exists predominantly as a 47 kDa nonglycosylated intracellular protein which can be induced to be secreted as 60 kDa glycoprotein. The glycosylated and unglycosylated forms of PAI-2 are equally effective as inhibitors of urokinase-type plasminogen activator (uPA), the only established physiological target of this serpin. PAI-2 has a unique ability to form dormant polymers spontaneously and reversibly under physiological conditions. The physiological relevance of this property, which is neither a consequence of any mutation in the PAI-2 gene nor associated with any known disorder, is still unclear. However, it appears that the formation of intracellular dormant polymers may be important for the controlled release of the inhibitor from PAI-2 producing cells. Plasma levels of PAI-2 are usually low or undetectable, except during pregnancy and in some forms of monocytic ...
1C5Q: Structural basis for selectivity of a small molecule, S1-binding, submicromolar inhibitor of urokinase-type plasminogen activator.
The PDB archive contains information about experimentally-determined structures of proteins, nucleic acids, and complex assemblies. As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
Urokinase Receptor deficient mice are deficient in skin wound healing and are protected from skin carcinogenesis: connection to skin stem cells ...
This trypsin-like integral-membrane serine peptidase has been implicated in breast cancer invasion and metastasis [1,2]. The enzyme can activate hepatocyte growth factor/scattering factor (HGF/SF) by cleavage of the two-chain form at an Arg residue to give active alpha- and beta-HGF, but It does not activate plasminogen, which shares high homology with HGF [1]. The enzyme can also activate urokinase plasminogen activator (uPA), which initiates the matrix-degrading peptidase cascade [1,2]. Belongs in peptidase family S1A ...
PLAU is a protease that converts plasminogen to plasmin. It appears to affect murine ageing: its overexpression in the brain diminishes food consumption and extends longevity probably through a mechanism similar to caloric restriction [13]. It is unclear at present whether PLAU affects human ageing, despite some evidence linking PLAU to age-related neurological diseases [374]. ...
The Her2+/uPA+ breast cancers are clinically the most aggressive, more so than the Her2+/uPA-, Her2-/uPA+, and Her2-/uPA- subtypes. Proteolytic modulation of He...
TY - JOUR. T1 - Tissue urokinase-type plasminogen activator receptor levels in breast cancer.. AU - Gong, S. J.. AU - Rha, SunYoung. AU - Chung, Hyuncheol. AU - Yoo, N. C.. AU - Roh, J. K.. AU - Yang, W. I.. AU - Lee, K. S.. AU - Min, J. S.. AU - Kim, B. S.. AU - Chung, H. C.. PY - 2000/9/1. Y1 - 2000/9/1. N2 - Cancer invasion is induced by several proteolytic enzyme systems associated with the destruction of basement membrane and extracellular matrix. Urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) have been reported as prognostic factors in breast cancer patients and plasminogen activation is regulated by various factors such as uPAR and growth factors. Thus, we examined the tissue levels of urokinase-type plasminogen activator receptor (uPAR) in breast cancer patients. Tissue uPAR levels were measured by ELISA assay in 268 breast cancer patients. The median and mean values of tissue uPAR level in breast cancer were 3.5 ng/mg cytosol protein and ...
TY - JOUR. T1 - Urokinase-type plasminogen activator receptor is involved in mediating the apoptotic effect of cleaved high molecular weight kininogen in human endothelial cells. AU - Cao, Dian J.. AU - Guo, Yan Lin. AU - Colman, Robert W.. PY - 2004/5/14. Y1 - 2004/5/14. N2 - Cleaved high molecular weight kininogen (HKa) has been shown to inhibit in vivo neovascularization and induce apoptosis of endothelial cells. We have shown that HKa-induced apoptosis correlated with its antiadhesive effect and was regulated by extracellular matrix (ECM) proteins. In this study, we identified the urokinase-type plasminogen activator receptor (uPAR) as a target of HKa activity at the endothelial cell surface. Anti-uPAR antibodies blocked the apoptotic effect of HKa. Further studies revealed that uPAR formed a signaling complex containing integrin αvβ3 or α5β1, caveolin, and Src kinase Yes in endothelial cells. HKa physically disrupted the formation of this complex in a manner that paralleled its ...
BACKGROUND: High levels of circulating forms of the urokinase-type plasminogen activator receptor (uPAR) are significantly associated to poor prognosis in cancer patients. Our aim was to determine biological variations and reference intervals of the uPAR forms in blood, and in addition, to test the clinical relevance of using these as cut-points in colorectal cancer (CRC) prognosis. METHODS: uPAR forms were measured in citrated and EDTA plasma samples using time-resolved fluorescence immunoassays. Diurnal, intra- and inter-individual variations were assessed in plasma samples from cohorts of healthy individuals. Reference intervals were determined in plasma from healthy individuals randomly selected from a Danish multi-center cross-sectional study. A cohort of CRC patients was selected from the same cross-sectional study. RESULTS: The reference intervals showed a slight increase with age and women had~20% higher levels. The intra- and inter-individual variations were ~10 % and ~20-30 %, ...
Dive into the research topics of Soluble urokinase-type plasminogen activator receptor, changes of 24-hour blood pressure, and progression of chronic kidney disease. Together they form a unique fingerprint. ...
A circulating biomarker of early pregnancy outcome independent of ultrasonography and gestational age is a coveted goal. This study evaluated soluble urokinase plasminogen activator receptor (suPAR), a well-described marker of inflammation and immunological activation, for this purpose, and compared it with established early pregnancy biomarkers of the luteoplacental phase: progesterone, estradiol and hCG. We merged data from two prospective first trimester cohorts to conduct a case-control study comparing these analytes in women who had either a live birth, a miscarriage or an ectopic pregnancy. The ability to predict pregnancy location and viability was assessed by areas under the receiver operating characteristic curves (AUC). Comparing women irrespective of gestational age with a live birth, miscarriage or ectopic pregnancy showed significantly lower suPAR values in the latter group (2.4 vs. 2.4 vs. 2.0 μg/L, p = 0.032, respectively), as were all other analytes. Before 6 weeks gestation, ...
Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, Feuer EJ, Thun MJ: Cancer statistics. CA Cancer J Clin 2005, 55:10-30. PubMed Abstract , Publisher Full Text - Greenwald P: Colon cancer overview. Cancer 1992, 70:1206-1215. PubMed Abstract , Publisher Full Text - 15. Fearon,E.R. and Vogelstein,B. (1990) A genetic model for colorectal tumorigenesis. Cell, 61, 759-767. Kohonen-Corish,M., Ross,V.L., Doe,W.F. et al. (1996) RNA-based mutation screening in hereditary nonpolyposis colorectal cancer. Am. J. Human Genet., 59, 818-824. - Muto T, Bussey HJR, Morson BC (1975) The evolution of cancer of the colon and rectum. Cancer 36:2251-2270. - Dahiya R, Yoon W, Boyle B, Schoenberg S, Yen T, Narayan P: Biochemical, cytogenetic, and morphological characteristics of human primary and metastatic prostate cancer cell lines. Biochem Int 1992, 27:567-577. PubMed Abstract - Mook ORF, Frederiks WM, Van Noorden CJF: The role of gelatinases in colorectal cancer progression and metastasis. Biochim Biophys ...
Re-epithelialization is a pivotal process in normal skin repair. Studies from knockout mice demonstrate that an intact plasminogen activator system is an essential requirement for this process and thus for wound healing. In this study, transgenic mice were generated overexpressing urokinase plasminogen activator (uPA) to assess the effect on cutaneous wound healing. Constitutive epidermal overexpression resulted in embryonic toxicity. However, mice generated with uPA under the inducible control of the Cre/LoxP system or K6 promoter (K6-uPAtg) facilitated effective uPA induction. Importantly, analysis of K6-uPAtg mice demonstrated a marked induction of functional uPA upon cutaneous wounding. Subsequent wounding analyses, however, showed no gross differences from wild-type wounds, suggesting that complex regulation of uPA occurs within cutaneous wounds. A key consequence of cutaneous wounding is the development of tissue hypoxia, a potent stimulus for increased keratinocyte migration and hence re- ...
We have raised four monoclonal antibodies recognizing different epitopes within the human cell-surface receptor for urokinase-type plasminogen activator (u-PA). One of these antibodies completely abolishes the potentiation of plasmin generation observed upon incubation of the zymogens pro-u-PA and plasminogen with U937 cells. This antibody, which is also the only one to completely inhibit the binding of DFP-inactivated [125I]-u-PA to U937 cells, is directed against the u-PA binding NH2-terminal domain of u-PAR, a well-defined fragment formed by limited chymotrypsin digestion of purified u-PAR, demonstrating the functional independence of the u-PA binding domain as well as the critical role of u-PAR in the assembly of the cell-surface plasminogen activation system. ...
Abcams Tissue type Plasminogen Activator ELISA Kit suitable for Cell culture supernatant, Saliva, Milk, Urine, Serum, Plasma, Tissue in human. Reliably…
Abstract: Plasminogen activator inhibitor-I plays a major role in the fibrinolytic system as the main physiological inhibitor of both tissue-type and urinary-type plasminogen activators. The inhibitor is present in plasma in small amounts and derives mainly from endothelial cells. Positive correlations have been reported between plasma levels and different parameters, such as serum triglycerides, insulin plasma levels and body mass index. Moreover, high plasma inhibitor concentrations have been observed in different disease states, but it must be stressed that plasminogen activator inhibitor-1 behaves as an acute-phase reactant and measurement of plasma levels is not significant in the acute phase of the disease. A possible predictive value of inhibitor levels for thrombotic events such as deep vein thrombosis and ischemic heart disease has been studied. On the basis of available studies, the predictive value is not clear for venous thrombosis, whereas plasminogen activator inhibitor-1 levels ...
Mounting evidence shows that the urokinase plasminogen activator (uPA) and its receptor (uPAR) play a central role in tumor progression. 120 h p.i. In vivo uPA specificity of 89Zr-Df-ATN-291 was confirmed by successful pharmacological blocking of tumor uptake with ATN-291 in U87MG tumors. Akap7 Although the detailed mechanisms behind [19], and more recently, an 111In-labeled antibody adopted for prostate cancer imaging with remarkable tumor accumulation [20]. Our goal was to investigate a novel probe for effective targeting and imaging of the uPA/uPAR system in cancer with excellent targeting specificity and image contrast. To achieve this goal, 89Zr-labeled Bortezomib ATN-291 (i.e., 89Zr-Df-ATN-291; Df is abbreviated for deferoxamine) was used as an immunoPET probe. 89Zr (t1/2 = 78.4 h) was selected as the radiolabel in this study to provide a longitudinal evaluation on the interaction between ATN-291 and different tumor types [21]. To accomplish this goal, various studies were carried out to ...
Results Full-length uPAR expression was significantly downregulated in SSc dermis, especially in fibroblasts and endothelial cells. Dermal thickness, collagen content and myofibroblast counts were significantly greater in uPAR−/− than in uPAR+/+ mice. In uPAR−/− mice, dermal fibrosis was paralleled by endothelial cell apoptosis and severe loss of microvessels. Lungs from uPAR−/− mice displayed non-specific interstitial pneumonia-like pathological features, both with inflammation and collagen deposition. Pulmonary pathology worsened significantly from 12 to 24 weeks, as shown by a significant increase in alveolar septal width and collagen content.. ...
2016 the American Physiological Society. Asthma is one of the most common respiratory diseases. Although progress has been made in our understanding of airway pathology and many drugs are available to relieve asthma symptoms, there is no cure for chronic asthma. Plasminogen activator inhibitor 1 (PAI-1), a primary inhibitor of tissuetype and urokinase-type plasminogen activators, has pleiotropic functions besides suppression of fibrinolysis. In this study, we show that administration of TM5275, an orally effective small-molecule PAI-1 inhibitor, 25 days after ovalbumin (OVA) sensitization-challenge, significantly ameliorated airway hyperresponsiveness in an OVAinduced chronic asthma model. Furthermore, we show that TM5275 administration significantly attenuated OVA-induced infiltration of inflammatory cells (neutrophils, eosinophils, and monocytes), the increase in the levels of OVA-specific IgE and Th2 cytokines (IL-4 and IL-5), the production of mucin in the airways, and airway subepithelial ...
The plasminogen activator (PA)/plasmin system is thought to be involved in processes such as tumor invasion and wound healing, during which epithelial and mesenchymal cells come close together. However, information on regulation of the PA/plasmin system during epithelial-mesenchymal interactions is scarce. Therefore, we examined the in vitro modulation of the production and activity of the components of the PA/plasmin system in squamous carcinoma cells (SCC-4) and normal human keratinocytes in relation to cell density and the presence or absence of fibroblasts (3T3 cells). There was an inverse relation between cell density and mRNA expression for urokinase-type plasminogen activator (u-PA) and u-PA receptor in both SCC-4 cells and keratinocytes. In addition, such a relation was found for plasminogen-activator inhibitor types 1 (PAI-1) and 2 (PAI-2) in SCC-4 monocultures, but not in keratinocyte monocultures. In contrast to monocultures, variation of cell density did not affect the mRNA ...
Purpose: A strong prognostic impact of urokinase type plasminogen activator (uPA) and its inhibitor plasminogen activator inhibitor type 1 (PAI-1) as individual factors is well established, with a level of evidence I according to the ASCO recommendations, and can be used in early breast cancer (EBC) adjuvant treatments discussions. However, the association or independence of these factors with other determinant clinicopathological parameters remains unclear in this setting. The independence or correlation of these factors in the adjuvant population is evaluated here. Patients and methods: 556 EBC patients operated between January 2006 and December 2009 (mastectomy, 99 patients; breast conservative surgery, 457 patients) were analyzed in this retrospective study. Inclusion criteria were: (i) patient curatively operated for EBC, (ii) no previous diagnosis of EBC or another malignant disease, (iii) no neoadjuvant treatment, (iv) no evidence of distant metastasis, (v) unilateral disease. Classical ...
Objective Inflammation and fibrosis are intertwined in multiple disease processes. We have previously found that over-expression of urokinase plasminogen activator in macrophages induces spontaneous macrophage accumulation and fibrosis specific to the heart in mice. Understanding the relationship between inflammation and fibrosis in the heart is critical to developing therapies for diverse myocardial diseases. Therefore, we sought to determine if uPA induces changes in macrophage function that promote cardiac collagen accumulation. Methods and Results We analyzed the effect of the uPA transgene on expression of pro-inflammatory (M1) and pro-fibrotic (M2) genes and proteins in hearts and isolated macrophages of uPA overexpressing mice. We found that although there was elevation of the pro-inflammatory cytokine IL-6 in hearts of transgenic mice, IL-6 is not a major effector of uPA induced cardiac fibrosis. However, uPA expressing bone marrow-derived macrophages are polarized to express M2 genes in
suPAR is a novel biomarker of inflammation, and it has been shown that suPAR is expressed in carotid plaque.10 In this study, we showed that elevated levels of suPAR were significantly associated with an increased risk of both CAD and ischemic stroke. Plasma levels of suPAR were increased in subjects with carotid plaque, and presence of both carotid plaque and elevated suPAR levels substantially increased risk of ischemic stroke and CAD.. Previous studies have shown that elevated levels of suPAR are related to increased risk of CVD.8,9 Our results are in accordance with a previous study that showed that suPAR in plasma was associated with carotid plaque and that subjects with elevated levels of suPAR had an increased risk of CVD.21 In a prospective study of 2315 healthy individuals, elevated suPAR, in combination with elevated hsCRP, improved the risk prediction beyond the Framingham risk score.22 To our knowledge, there are no studies that have explored the relationship with ischemic ...
0 (Radioisotopes), 21829-25-4 (Nifedipine), 55-63-0 (Nitroglycerin), 7440-28-0 (Thallium), Clinical Trials, Coronary Circulation, Coronary Vessels, EC 3.4.- (Streptokinase), EC 3.4.21.73 (Urinary Plasminogen Activator), Fibrinolysis, Heart/*radionuclide imaging, Human, Myocardial Contraction, Myocardial Infarction/*drug therapy/radionuclide imaging, Nifedipine/therapeutic use, Nitroglycerin/therapeutic use, Pilot Projects, Radioisotopes/*diagnostic use, Random Allocation, Streptokinase/administration & dosage/*therapeutic use, Stroke Volume, Thallium/*diagnostic use, Urinary Plasminogen Activator/therapeutic use ...
article{25b1f445-f908-4d68-b75c-46e879dc6bc1, abstract = {volved in tumor growth and metastasis. We assayed the components of the uPA system in homogenates of 64 primary epithelial ovarian tumors and 5 metastases and evaluated the association of these parameters to prognosis in the 51 malignant cases. The levels of uPA, PAI-2 and the uPA: PAI-I complex increased with progressive loss of histological differentiation (P-trend <0.001, <0.05 and <0.001). The level of PAI-I was higher in poorly than in well/moderately differentiated tumors (p = 0.03). The content of uPAR was lower in benign tumors as compared to borderline malignancies (p = 0.002), invasive primary tumors (p < 0.001), and metastases (p = 0.002). Surprisingly, the level of uPAR was lower in poorly differentiated as compared to both borderline (p = 0.01) and well differentiated malignant tumors (p = 0.005). Also, the level of uPAR was lower in advanced as compared to early stages of the disease (P-trend = 0.002). The median ...
1. Brummel-Ziedins K, Orfeo T, Swords JN et al. Blood coagulation and fibrinolysis. In: Greer JP, Foerster J, Rodgers JM et al (eds). Wintrobes Clinical Hematology. Baltimore: Lippincott Wiliams & Wilkins 2009: 528-619. 2. Schmitt M, Harbeck M, Thomssen C et al. Clinical impact of the plasminogen activation system in tumor invasion and metastasis: Prognostic relevance and target therapy. Thromb Haemost 1997; 78: 285-296. 3. Silverman GA, Bird PI, Carrell RW et al. The serpins are an expanding superfamily of structurally similar but functionally diverse proteins: evolution, mechanism of inhibition, novel functions, and a revised nomenclature. J Biol Chem 2001; 276: 33293-33296. 4. De Bruin PA, Griffioen G, Verspaget HW et al. Plasminogen activators and tumor development in the human colon: activity levels in normal mucosa, adenomatous polyps, and adenocarcinomas. Cancer Res 1987; 47: 4654-4657. 5. Duffy MJ. The urokinase plasminogen activator system: role in malignancy. Curr Pharm Des 2004; 10: ...
en] The plasminogen (Plg)/plasminogen activator (PA) system plays a key role in cancer progression, presumably via mediating extracellular matrix degradation and tumor cell migration. Consequently, urokinase-type PA (uPA)/plasmin antagonists are currently being developed for suppression of tumor growth and angiogenesis. Paradoxically, however, high levels of PA inhibitor 1 (PAI-1) are predictive of a poor prognosis for survival of patients with cancer. We demonstrated previously that PAI-1 promoted tumor angiogenesis, but by an unresolved mechanism. We anticipated that PAI-1 facilitated endothelial cell migration via its known interaction with vitronectin (VN) and integrins. However, using adenoviral gene transfer of PAI-1 mutants, we observed that PAI-1 promoted tumor angiogenesis, not by interacting with VN, but rather by inhibiting proteolytic activity, suggesting that excessive plasmin proteolysis prevents assembly of tumor vessels. Single deficiency of uPA, tissue-type PA (tPA), uPA ...
Macrophage inhibitory cytokine-1 induces the invasiveness of gastric cancer cells by up-regulating the urokinase-type plasminogen activator system / Dong Hoon Lee; Young Yang; S J Lee; Kun Yong Kim; Tae Hyeon Kim; Sun Mi Shin; K S Song; Y H Lee; Y J Kim; Jung Joon Lee; In Pyo Choi; Jeong-Hyung Lee , 2003 ...
Background Mesenchymal stem cells produced from adipose tissue (ADSC) are multipotent stem cells, comes from the vascular-stromal compartment of unwanted fat tissue. growth aspect (TGF-) elevated in the previous ADSC but was decreased by hypoxia. Appearance of anti-angiogenic elements including thrombospondin-1 (TBS1) and plasminogen activator inhibitor-1 (PAI-1) do increase in previous ADSC, but could possibly be decreased by hypoxic arousal. Endostatin (ENDS) was the best in aged ADSC and was also down-regulated by hypoxia. We observed higher gene appearance of proteases program elements like urokinase-type plasminogen activator receptor (uPAR), matrix metalloproteinases (MMP2 and MMP9) and PAI-1 in aged ADSC in comparison to youthful ADSC, however they reduced in previous ADSC. Tube development on matrigel was higher in the current presence of conditioned moderate from youthful ADSC compared to aged ADSC. Conclusions ADSC isolated from old pets present adjustments, including impaired order ...
Although extracellular (glycosylated) PAI-2 functions to regulate fibrinolysis, it remains unclear whether this inhibitory role is the main function of PAI-2. PAI-2 is predominantly intracellular. The secretory signal peptide of PAI-2 is relatively inefficient, perhaps by evolutionary design, as various mutations to the signal sequence can significantly enhance secretion efficiency.[10] PAI-2 is undetectable in adult plasma, and is typically only detectable during pregnancy, in myelomonocytic leukemias, or in gingival crevicular fluid; moreover, PAI-2 is a slower inhibitor than its counterpart PAI-1 by orders of magnitude (based on second order rate constants).[13] On the other hand, detailed intracellular roles for PAI-2 have not yet been conclusively established. PAI-2 is upregulated during both pregnancy and immune responses. During pregnancy, PAI-2 is particularly present in the decidua and amniotic fluid, where it may protect membranes from digestion and aid in remodeling fetal and uterine ...
NOVOA HERRAN, Sandra Susana; CASTELBLANCO, Mariela; SANCHEZ -GOMEZ, Myriam e UMANA PEREZ, Adriana. TRANSFORMING GROWTH FACTOR BETA HAS DUAL EFFECTS ON MMP9 AND uPA EXPRESSION IN HTR-8/SVneo HUMAN TROPHOBLASTIC CELL LINE. Acta biol.Colomb. [online]. 2019, vol.24, n.1, pp.26-37. ISSN 0120-548X. https://doi.org/10.15446/abc.v24n1.69527.. Invasion of trophoblast into endometrium is vital for successful pregnancy development. MMP9 and uPA are key proteases in this process, but it is still not clear the regulation of its expression by Transforming Growth Factor Beta (TGF-β), a known negative regulator of trophoblast invasion. We evaluated the effect of TGF-β on the transcriptional expression of uPA and MMP9 over time, in HTR-8/SVneo trophoblast cells cultured with or without 0.5 % fetal bovine serum, via RT qPCR. The involved transcription factors and signaling pathways were analyzed in silico, using Proscan, Enrich, PCViz and Wiki Pathway. Results showed that TGF-β temporarily regulates the ...
PAI-1s main function entails the inhibition of urokinase plasminogen activator (uPA), an enzyme responsible for the cleavage of plasminogen to form plasmin. Plasmin mediates the degradation of the extracellular matrix either by itself or in conjunction with matrix metalloproteinases. In this scenario, PAI-1 inhibits uPA via active site binding, preventing the formation of plasmin. Additional inhibition is mediated by PAI-1 binding to the uPA/uPA receptor complex, resulting in the latters degradation.[2] Thus, PAI can be said to inhibit the serine proteases tPA and uPA/urokinase, and hence is an inhibitor of fibrinolysis, the physiological process that degrades blood clots. In addition, PAI-1 inhibits the activity of matrix metalloproteinases, which play a crucial role in invasion of malignant cells through the basal lamina. PAI-1 is mainly produced by the endothelium (cells lining blood vessels), but is also secreted by other tissue types, such as adipose tissue. ...
The protease uPA and its inhibitor PAI-1 play major roles in hemostasis and are also involved in cancer progression. This is mainly caused by their ability to degrade extracellular matrix-facilitating tumor cell migration. This study aimed to investigate the impact of uPA/PAI-1 and disseminated cytokeratin-positive cells (dCK+) on the outcome and the existence of synergistic effects. We retrospectively analyzed a cohort of 480 breast cancer cases with known uPA/PAI-1 and dCK+ status. uPA/PAI-1 was tested on fresh tumor samples using a commercial ELISA test. Bone marrow aspirates were investigated immunocytochemically for CK18. DCK+ cells were identified in 23% of cases. uPA positivity was significantly associated with the occurrence of dCK+ cells (P = 0.028). uPA and PAI-1 were significantly associated with outcome in the subgroup of early-stage cases without chemotherapy. DCK+ cells alone were not prognostic. However, we found synergistic effects. In the subgroup of node-negative cases with and without
Helseth, E.; Dalen, A.; Unsgaard, G.; Vik, R., 1988: Type beta transforming growth factor and epidermal growth factor suppress the plasminogen activator activity in a human glioblastoma cell line
INTRODUCTION: The regulation of extracellular proteolytic activity via the plasminogen activation system is complex, involving numerous activators, inhibitors and receptors. Previous studies on monocytic and colon cell lines suggest that plasmin pre treatment can increase plasminogen binding, allowing the active enzyme to generate binding sites for its precursor. Other studies have shown the importance of pre formed receptors such as annexin II heterotetramer. However, few studies have utilised techniques which exclusively characterise cell surface events and these mechanisms have not been investigated at the breast cancer cell surface. METHODS: We have studied plasminogen binding to MCF 7 in which uPAR levels were upregulated by PMA stimulation allowing flexible and transient modulation of cell surface uPA. Similar experiments were also performed using MDA MB 231, which overexpress uPAR/uPA endogenously. Using techniques which preserve cell integrity, we characterize the role of uPA as both a
Systemic levels of soluble urokinase-type plasminogen activator receptor (suPAR) positively correlate with the activation level of the immune system. We reviewed the usefulness of systemic levels of s
Lv L, Wang F, Wu L, Wang JW, Cui Z, Hayek SS, Wei C, Reiser J, He K, Zhang L, Chen M, Zhao MH. Soluble urokinase-type plasminogen activator receptor and incident end-stage renal disease in Chinese patients with chronic kidney disease. Nephrol Dial Transplant. 2020 03 01; 35(3):465-470 ...
A65 The urokinase plasminogen activator receptor (uPAR) has been implicated in a number of processes that contribute to tumor progression and metastasis including tumor cell proliferation, invasion, adhesion and angiogenesis. Thus, uPAR represents an attractive therapeutic target for the treatment of cancer. We have developed a novel antibody, ATN-658, that targets uPAR. In contrast to previous therapeutic approaches targeting uPAR, ATN-658 does not inhibit the binding of uPA to uPAR and can bind to uPAR regardless of whether it is occupied by uPA. In addition, ATN-658 can bind to the residual fragment of uPAR frequently observed in tumors that remains attached to the membrane after proteolysis. We have previously demonstrated that ATN-658 significantly inhibited pancreatic cancer growth, invasion and metastasis in an orthotopic xenograft model (Bauer et al., Cancer Res 65:7775-81, 2005). In this study, we extend the results obtained in this pancreatic cancer model to a model of colon cancer ...
Aims: Receiver operating characteristic (ROC) curve analysis is a well-established method to study the accuracies of biological markers. It may, however, be suboptimal for analysing outcomes over time, such as prognosis. Here, the clinical value of time-dependent ROC curve analysis for improving the identification of high-risk patients with colon cancers and diffuse large B-cell lymphomas (DLBCL) is explored.. Methods: Using tissue microarrays, immunohistochemistry was performed on two matched sets (N = 469, each) of colon cancers (p53, CD8+ tumour infiltrating lymphocytes (TILs), mammalian sterile-like 20 kinase 1 (MST1), mucin 2 (MUC2) and urokinase plasminogen activator receptor (uPAR)) and on 208 DLBCL (Bcl2, Bcl6, CD10, FOXP1 and Ki67). The area-under-the-curve (AUC)-over-time plots, cut-off scores for tumour marker positivity and Kaplan-Meier survival curves were analysed.. Results: With the exception of uPAR, all markers were most accurate within the first 18 months following diagnosis. ...
Disputas 22.april 2009.. Clinicopathological significance of seprase, dipeptidyl peptidase IV and urokinase-type plasminogen activator in esophageal carcinomas ...
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A novel plasminogen activator which is identical in peptide sequence to naturally occurring human prourokinase except that the 155th amino acid counting from the N-terminal amino acid (serine) is othe
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Two-site ELISA method for the measurement of uPA-PAI-1 complexes. Assay designed with a Murine monoclonal antibody specific for uPA for coating, and capturing uPA-PAI-1 complexes, and a Murine monoclonal antibody, specific for PAI-1 and labeled with a Horse Radish Peroxidase (HRP) marker. The assay only measures uPA complexed with PAI-1.
In this proposal, these researchers would like to use the SPECTROstar Nano optical absorbance plate reader for further evaluation of the effects of ssDNA, dsDNA and oligonucleotides on the activation of plasminogen (PLG) by tissue (tPA) and urokinase plasminogen (uPA). The major goals of this project include characterizing the template mechanism of DNA-assisted PLG activation by tPA and uPA and then developing a micro assay for measuring the rates of PLG activation using the SPECTROstar Nano and the low volume LVis plate. The researchers conclude, …this proposal would benefit not only the fields of molecular mechanisms of fibrinolysis, PLG activation and fibrinolytic therapy, but also give a rigorous field test of this novel product ...
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The improvement of the healing rates for breast cancer is based to an important part on the consistent use of so-called adjuvant (supporting ) medicam
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