• This is evident by the significantly higher affinity of CXCL12 binding to ACKR3/CXCR7 compared to CXCR4, along with its constant internalization facilitated by the recruitment of β-arrestin, without known downstream signaling events. (wikipedia.org)
  • ACKR3 and CXCR4 have been shown to interact, different possibilities regarding the involvement of ACKR3 and CXCR4 in CXCL12 signaling: A) ACKR3 can attenuate CXCR4 signaling by forming heterodimers with CXCR4. (wikipedia.org)
  • C) Synergistic effects between CXCR4 and ACKR3 have been observed in many cases, suggesting that cellular responses to CXCL12 require the presence of both receptors. (wikipedia.org)
  • CXCL12 is a constitutively expressed chemokine which binds primarily to the CXCR4 receptor and regulates cell growth, chemotaxis, myelopoiesis, lymphopoiesis, and development of the nervous and cardiovascular systems. (haematologica.org)
  • 6 Recent animal studies involving systemic injection of labeled MM plasma cells have also demonstrated that blocking the CXCL12/CXCR4 axis leads to a 20% reduction in bone marrow tumor burden. (haematologica.org)
  • We found that 4T1 breast cancer cells expressed high levels of CXCR7, but not of CXCR4, both of which are CXCL12 receptors. (elsevierpure.com)
  • The chemokine CXCL12 (stromal cell-derived factor-1, SDF-1) and its receptor CXCR4 play a major role in tumor initiation, promotion, progression and metastasis, especially for breast cancer cells. (cell-signaling-pathways.com)
  • d This anti-apoptotic effect could be reversed by co-incubation with the CXCR7-selective antagonist CCX733 (0.1?M) but not significantly by CXCR4-selective antagonist AMD3100 (5?M). Both antagonists experienced no inhibitory effects on their own (not shown). (cell-signaling-pathways.com)
  • Here, we report that CXCR4/CXCL12 signaling impacts enamel progenitor cell proliferation and motility in dental stem cell niche cells. (elsevierpure.com)
  • We then performed gain- and loss-of-function analyses to better elucidate the role of CXCR4 and CXCL12. (elsevierpure.com)
  • CXCR4-deficient mice contain epithelial cell aggregates, while cell proliferation in mutant incisors was also significantly reduced. (elsevierpure.com)
  • We demonstrate in vitro that dental epithelial cells migrate toward sources of CXCL12, whereas knocking down CXCR4 impaired motility and resulted in formation of dense cell colonies. (elsevierpure.com)
  • These results suggest that CXCR4 expression may be critical for activation of enamel progenitor cell division and that CXCR4/CXCL12 signaling may control movement of epithelial progenitors from the dental stem cell niche. (elsevierpure.com)
  • CXC chemokine receptor 4 (CXCR4) and its ligand CXCL12, both of which are overexpressed in many cancers, play a pivotal role in metastasis. (biomedcentral.com)
  • Coexpression of LPA 1 with CXCR4 reduced CXCL12-mediated cAMP inhibition, ERK activation, Gα i/o activation, and β-arrestin recruitment, while CXCL12 binding to CXCR4 remained unaffected. (biomedcentral.com)
  • The addition of lysophosphatidic acid (LPA) further hindered CXCL12-induced Gα i/o recruitment to CXCR4. (biomedcentral.com)
  • LPA or alkyl-OMPT inhibited CXCL12-induced migration in various cancer cells that endogenously express both CXCR4 and LPA 1 . (biomedcentral.com)
  • Ultimately, complete inhibition of cell migration toward CXCL12 and alkyl-OMPT was only achieved in the presence of both CXCR4 and LPA 1 antagonists. (biomedcentral.com)
  • The presence and impact of CXCR4-LPA 1 heteromers on CXCL12-induced signaling and cell migration have been evidenced across various cell lines. (biomedcentral.com)
  • Safety appeared to be mediated, to some extent, through CXCL12 (SDF-1)/CXCR4 signaling. (signalingmolecule.com)
  • Cxcl12 appeared to cause the hyper-responsiveness of c-fibers by activating Cxcr4 [ 6 ]. (imrpress.com)
  • CXCR4 is the receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation. (thermofisher.com)
  • The combined treatment reduced CXCR4, CXCL12 and PD-L1 expression in MC38 tumors. (biomedcentral.com)
  • Dissection of PIM serine/threonine kinases in FLT3-ITD-induced leukemogenesis reveals PIM1 as regulator of CXCL12-CXCR4-mediated homing and migration. (ox.ac.uk)
  • PIM1-deficient bone marrow showed defects in homing and migration and displayed decreased surface CXCR4 expression and impaired CXCL12-CXCR4 signaling. (ox.ac.uk)
  • Through small interfering RNA-mediated knockdown, chemical inhibition, expression of a dominant-negative mutant, and/or reexpression in knockout cells, we found PIM1 activity to be essential for proper CXCR4 surface expression and migration of cells toward a CXCL12 gradient. (ox.ac.uk)
  • In primary leukemic blasts, high levels of surface CXCR4 were associated with increased PIM1 expression, and this could be significantly reduced by a small molecule PIM inhibitor in some patients. (ox.ac.uk)
  • Recently, it has been found that both chemokine C-X-C motif ligand 12 (CXCL12) and its receptor CXCR4 were upregulated in spinal glial cells of mice with partial sciatic nerve ligation (pSNL)-induced neuropathic pain or chronic post-ischemia-induced inflammatory pain [ 5 ]. (biomedcentral.com)
  • The CXCR4/CXCL12 axis plays a role in cancer metastases, stem cell mobilization and chemosensitization. (cnr.it)
  • A three amino acid motif (Ar-Ar-X) in CXCL12, also found in the reverse orientation (X-Ar-Ar) in the vMIP-II inhibitory chemokine formed the core of nineteen cyclic peptides evaluated for inhibition of CXCR4-dependent migration, binding, P-ERK1/2-induction and calcium efflux. (cnr.it)
  • Peptides R, S, and T significantly reduced the association of the 12G5-CXCR4 antibody to the receptor and inhibited CXCL12-induced calcium efflux. (cnr.it)
  • Moreover, CXCR4\specific ligand, CXCL12, enhanced cellular proliferation, migration, colony formation and invasion in CXCR4\overexpressing and similarly in miR\9 knockdown cells. (irjs.info)
  • MiR\9 knockdown, similar to CXCR4 overexpression, significantly promoted aggressive HNSCC tumour cell characteristics. (irjs.info)
  • The CXCR4-CXCL12-Axis Is of Prognostic Relevance in DLBCL and Its Antagonists Exert Pro-Apoptotic Effects In Vitro. (tugraz.at)
  • Within the BM, CXCL12 is constitutively produced at higher levels by different BM stromal niche cells and plays an important function within the homing and retention of HSPCs.78,79 The conditional deletion of CXCR4 or CXCL12 outcomes in significantly increased HSPC numbers inside the peripheral blood and spleen.79 Via the downregulation of CXCR4 on HSPCs along with the alteration of your plasmato-marrow CXCL12 gradient, the CXCR4 agonist peptide. (calcimimeticagent.com)
  • Importantly, elevated CXCR7 and depressed CXCL12 expression levels were prominent features of clinical breast cancer lesions and were related significantly with poor survival. (elsevierpure.com)
  • The levels of several chemokines were significantly higher in intervillous compared to peripheral blood, including macrophage migration inhibitory factor (MIF), CXCL10, and CCL25, whereas CCL21, CCL27 and CXCL12 were lower. (frontiersin.org)
  • It is now classified as a chemokine receptor able to bind the chemokines CXCL12/SDF-1 and CXCL11. (wikipedia.org)
  • 6 , 7 CXCL12 is an important mediator of several aspects of MM biology including transendothelial migration, 8 , 9 MM plasma cell migration and retention within the bone marrow, 10 , 11 angiogenesis, 7 and osteoclastic bone resorption. (haematologica.org)
  • Tan II A reduced CXCL12-induced A375 cell invasive ability and migration in a dose dependent manner. (biomedcentral.com)
  • Conversely, CXCL12-induced calcium signaling and migration were increased in LPAR1 knockout cells, and LPA 1 -selective antagonists enhanced CXCL12-induced Gα i/o signaling and cell migration in the parental MDA-MB-231 cells but not in LPA 1 -deficient cells. (biomedcentral.com)
  • The four peptides efficiently inhibited CXCL12-dependent migration at concentrations as low as 10 nM and delayed CXCL12-mediated wound healing in PES43 human melanoma cells. (cnr.it)
  • Importantly, the pro-survival, proliferative, chemoresistant and activation effects promoted by the microenvironment were abrogated by TAK-659, which furthermore blocked CLL cell migration toward BMSC, CXCL12, and CXCL13. (uab.cat)
  • Whereas some reports claim that the receptor induces signaling following ligand binding, recent findings in zebrafish suggest that CXCR7 functions primarily by sequestering the chemokine CXCL12. (wikipedia.org)
  • Despite being considered atypical, the functions of ACKR3 do not imply that it acts as a completely inactive receptor for CXCL12. (wikipedia.org)
  • Nevertheless, its role as a decoy receptor for CXCL12/SDF1 is well-established. (wikipedia.org)
  • Upregulated DEGs were significantly involved in immune response, MHC class II receptor activity, and presented in the extracellular region, while downregulated DEGs were mainly enriched in response to organic substances, extracellular region parts, and cadmium ion binding. (edu.au)
  • p53 initial by simply Nutlin-3a wasn't cytotoxic to stromal cellular material, nevertheless decreased CXCL12 mRNA levels along with secretion of CXCL12 somewhat via p53-mediated HIF-1 alpha dog down-regulation. (signalingmolecule.com)
  • pSNL-induced neuropathic pain significantly reduced mRNA expression of miR-23a. (biomedcentral.com)
  • The oncogenic CXCL12 mRNA and protein were more highly expressed in residual cancer cells from a hepatoma heterotopic murine tumor microenvironment and coculture of human hepatoma Huh7 and normal IMR90 cells after radiation. (molcells.org)
  • The expression of CXC chemokine ligand 12 (CXCL12) in bone marrow stromal cells, which plays a critical role in the maintenance of hematopoietic stem cells and also in cancer cell homing to bone, was markedly decreased in mice treated with G-CSF. (figshare.com)
  • In addition, flow cytometry on fresh B16-hCXCR4 tumors showed significantly higher Tregs number following anti-PD-1 partially reversed by the combined treatment Pep R and anti-PD-1. (biomedcentral.com)
  • The role of hypoxia-inducible factors-1 and -2 in the regulation of CXCL12 expression was examined using over-expression and short hairpin RNA knockdown constructs, electrophoretic mobility shift assays and chromatin immunoprecipitation. (haematologica.org)
  • The CXCL12 gene is located on long arm of chromosome 10 and was first cloned from a bone marrow-derived stromal cell line and then, identified as pre-B cell growth stimulating factor [ 10 ]. (biomedcentral.com)
  • SDF-1α(Stromal-Derived Factor-1α) or CXCL12 is a member of C-X-C chemokine family that its important role in recruitment of progenitor and stem cells from bone marrow to peripheral blood after injury and inflammation has been approved in many studies. (ijwph.ir)
  • The defensive aftereffect of stromal cells was significantly diminished by simply pre-exposure to the HDM2 chemical Nutlin-3a. (signalingmolecule.com)
  • Stromal desmin expression was significantly greater in stage III tumors when in contrast to the two stage I and II tumors, P 0. (mi-rna.com)
  • These results suggest that G-CSF suppressed cancer cell homing to bone by downregulating CXCL12 expression in bone marrow stromal cells, whereas G-CSF stimulated the progression of bone metastases at least in part by MDSC-mediated mechanisms. (figshare.com)
  • Results show that p53 activation within stroma cellular material blunts stroma cell-mediated potential to deal with FLT3 inhibition, to some extent via down-regulation involving CXCL12. (signalingmolecule.com)
  • The expressions of CCL21 and CXCL12 were also increased in lymph nodes from arsenic-treated WT mice. (eur.nl)
  • The administration of a neutralizing antibody against CCL21, but not CXCL12, abolished the increase of LCs in lymph nodes in vivo. (eur.nl)
  • After exposure to CXCL12 or CXCL11, the receptors were rapidly internalized alone or in close proximity. (cell-signaling-pathways.com)
  • This co-internalization was observed either with CXCL11 as the CXCR7-selective ligand (e-h) or with CXCL12 as YIL 781 the ligand for both receptors (i-l). (cell-signaling-pathways.com)
  • As seen best in immunofluorescence, CXCL12 activation initially resulted in a mostly individual internalization of both receptors (5?min, Fig.?2c, place) as detected by individual red and green dots and a lower frequency of yellow (merged fluorescence) dots. (cell-signaling-pathways.com)
  • In presence of CXCL12, CXCR7 expression on tumour cells was decreased. (elsevierpure.com)
  • Therefore, our data demonstrated that sustained expression of CXCL12 by MSCs in the primary tumour site inhibits metastasis through reduction of CXCR7, while, in the presence of TGFβ, this CXCL12 effect of MSCs on tumour cells is relieved. (elsevierpure.com)
  • Furthermore, the CXCL12 ligand is present in mesenchymal cells adjacent to the apical bud. (elsevierpure.com)
  • The expression of SDF-1 is significantly associated with tumor size and FIGO histology grade. (medscimonit.com)
  • The expression of NF-κB is significantly associated with tumor size, FIGO histology grade, and lymph node metastasis. (medscimonit.com)
  • The combined treatment, Pep R plus anti-PD-1, reduced the MC38 Relative Tumor Volume (RTV) by 2.67 fold ( p = 0.038) while nor anti-PD-1, neither Pep R significantly impacted on tumor growth. (biomedcentral.com)
  • In the B16-hCXCR4 tumors, two weeks of combined treatment reduced tumor volume by 2.27 fold while nor anti-PD-1 neither Pep R significantly impacted on tumor growth. (biomedcentral.com)
  • Taken together, radiation-induced histone alterations at the CXCL12 promoter in hepatoma cells are linked to CXCL12 upregulation and increased aggressiveness in the tumor microenvironment. (molcells.org)
  • Depletion of MDSCs using anti-Gr-1 antibody treatment significantly decreased the metastatic tumor burden in bone. (figshare.com)
  • In contrast, when G-CSF treatment was started after the tumor cells had homed to bone, G-CSF significantly accelerated bone metastases formation. (figshare.com)
  • 3 - 5 CXCL12 is highly expressed by MM plasma cells, 6 and circulating levels of CXCL12 are higher in the peripheral blood of MM patients than in age-matched normal donors and MGUS patients. (haematologica.org)
  • The CXCL12-3'A allele is associated with a higher mobilization yield of CD34 progenitors to the peripheral blood of healthy donors for allogeneic transplantation. (cdc.gov)
  • At week 12, only plasma CXCL5 ( P =0.021) and CXCL8 ( P =0.015) were significantly decreased compared to placebo. (naturalmedicinejournal.com)
  • In addition, 10 hub genes including CXCL12, CXCL8, CCL20, and CCL4 were found in the PPI network and module construction. (edu.au)
  • Conversely, miR\9 knockdown significantly increased both these features. (irjs.info)
  • Over-expression of hypoxia-inducible factor in multiple myeloma plasma cells strongly induced in vivo angiogenesis, and administration of a CXCL12 antagonist decreased hypoxia-inducible factor-induced angiogenesis. (haematologica.org)
  • Promoter analyses revealed increased hypoxia-inducible factor-2 binding to the CXCL12 promoter under hypoxic conditions. (haematologica.org)
  • The positive SDF-1or NF-κB expression is significantly correlated with poor prognosis. (medscimonit.com)
  • While the mechanisms responsible for aberrant plasma cell expression of CXCL12 remain to be determined, studies in other systems suggest a role for hypoxia and hypoxia-inducible transcription factors. (haematologica.org)
  • Prolonged exposure to hypoxia strongly up-regulated CXCL12 expression in multiple myeloma plasma cells and hypoxia-inducible factor-2 was found to play a key role in this response. (haematologica.org)
  • Conclusions Hypoxia-inducible factor-2 is a newly identified regulator of CXCL12 expression in multiple myeloma plasma cells and a major contributor to multiple myeloma plasma cell-induced angiogenesis. (haematologica.org)
  • The eutopic endometrium had significantly higher expression of CCL17 compared to normal endometrium, and the ectopic tissues had the highest expression. (endometriosi.it)
  • In comparison to BM-MSCs without osteoinductive treatment, gene expression in e-MSCs was significantly altered in terms of their cell adhesion- and chemotaxis-related profiles, as identified with Gene Ontology and Gene Set Enrichment Analysis. (elsevierpure.com)
  • Noteworthy, expression of the hematopoiesis-associated molecules CXCL12 and vascular cell adhesion molecule 1 was remarkably decreased in e-MSCs. (elsevierpure.com)
  • Histone demethylase inhibitor IOX1 attenuated CXCL12 expression and the malignant subpopulation, suggesting that responses to IR can be partially mediated via histone modifications. (molcells.org)
  • In addition to CXCL12, ACKR3 engages with multiple ligands, encompassing CXCL11, macrophage inhibitory factor (MIF), adrenomedullin (ADM), opioid peptides such as nociceptin, dynorphin, and enkephalin, as well as the viral chemokine vCCL2/viral macrophage inflammatory protein-II. (wikipedia.org)
  • c Both chemokine ligands, namely 5 nM CXCL11 and 1 nM CXCL12, significantly reduced staurosporine-induced apoptosis. (cell-signaling-pathways.com)
  • Overexpression of miR\9 in HNSCC cell lines significantly decreased cellular proliferation and inhibited colony formation in soft agar. (irjs.info)
  • Specialized medical outcomes using FLT3 inhibitor monotherapy have demostrated which bone marrow replies are normally significantly less distinct as compared to side-line bloodstream reactions. (signalingmolecule.com)
  • Similarly, LPS-stimulated IL-1 β release from whole blood was significantly enhanced in ethanol-fed mice. (uni-frankfurt.de)
  • Ninety-six hours after OVA sensitization, Langerin +EpCAM + cells in arsenic-treated WT mice were significantly increased in draining lymph nodes and decreased in epidermis without changes in the dermis. (eur.nl)
  • Interestingly, we found that MSC-produced CXCL12, an important chemokine in tumour metastasis, was markedly inhibited by TGFβ. (elsevierpure.com)
  • Transplant outcomes of the triple-negative NPM1/FLT3-ITD/CEBPA mutation subgroup are equivalent to those of the favourable ELN risk group, but significantly better than the intermediate-I risk group after allogeneic transplant in normal-karyotype AML. (cdc.gov)
  • This pattern appears to be a common arrangement of the CXCL12 system in various types of stem and progenitor cells. (wikipedia.org)
  • Among which CXCL12 stands out, due to its pro-inflammatory features, acting as chemoattractant recruiting immune cells. (biomedcentral.com)
  • The mechanism of action of ILP100-Topical was also confirmed when the treatment resulted in increased CXCL12-positive cells in the wounds, as well as increased blood flow around the wounds during the healing phase. (expertsvar.se)
  • All three peptides significantly inhibited subcutaneous growth of SN12C-EGFP renal cancer cells. (cnr.it)
  • Plerixafor blocks CXCL12 induced increase in proliferation in miR\9 knockdown cells. (irjs.info)
  • Combination of TAK-659 with other BCR inhibitors showed synergistic effect in inducing apoptosis, and the sequential addition of TAK-659 in ibrutinib-treated CLL cells induced significantly higher cytotoxicity. (uab.cat)
  • A significantly higher proportion of healed wounds (p=0.020) was seen on day 32 using multi-dose ILP100-Topical compared to saline and placebo (76% (73/96) and 59% (57/96) healed wounds respectively) when the results from the multi-dose-treated wounds were pooled. (expertsvar.se)
  • Recently, the investigation of the plasma of patients with diabetes revealed that patients with PDN had significantly higher level of methylglyoxal than patients without pain. (imrpress.com)
  • [ 6 ] In this study, the incidence of BPD was significantly higher in infants who had leukemoid reaction compared with those without leukemoid reaction. (medscape.com)
  • However, to date, there is no study between CXCL12 rs1801157 polymorphism and HPV infection as well as cervical lesions development. (biomedcentral.com)
  • Studies from our laboratory suggest a role for the CXCL12 chemokine in this process, with circulating levels of CXCL12 correlating with bone marrow angiogenesis in patients with multiple myeloma. (haematologica.org)
  • However, LPS significantly increased IL-6 and TNF-α levels. (uni-frankfurt.de)
  • The serum SDF-1α levels in the exposed participants with severe pulmonary complications was significantly lower than in controls(p=0.054). (ijwph.ir)
  • Several polymorphisms were identified in CXCL12 gene including rs1801157 in the 3′-untranslated region, which is characterized by a substitution of a guanine for an adenine. (biomedcentral.com)
  • The hypoxic regulation of CXCL12 was examined in multiple myeloma plasma cell lines using polymerase chain reaction and western blotting. (haematologica.org)
  • Results of KEGG analysis indicated that the upregulated DEGs mainly existed in cell adhesion molecules (CAMs), while downregulated DEGs were significantly involved in the MAPK signaling pathway. (edu.au)
  • The study showed a significantly positive correlation between the frequency of blood cultures positive for Streptococcus pneumoniae and the WBC and absolute neutrophil counts. (medscape.com)
  • The results showed miR\9 to be significantly downregulated in patients with poor treatment outcome, indicating its role as a potential biomarker in HNSCC. (irjs.info)
  • Epidemiological and clinical studies have suggested that cancer could be prevented or significantly reduced by treatment with anti-oxidant and anti-inflammatory drugs, therefore, curcumin, a principal component of turmeric (a curry spice) showing strong anti-oxidant and anti-inflammatory activities, might be a potential candidate for the prevention and/or treatment of cancer and other chronic diseases. (blogspot.com)
  • In several controlled preclinical models, the research team behind the new study has previously demonstrated accelerated wound healing after topical treatment (treatment on the skin) using lactic acid bacteria, or Limosilactobacillus reuteri, genetically modified to produce the chemokine CXCL12 (ILP100-Topical). (expertsvar.se)
  • The results show that treatment using ILP100-Topical was safe and well tolerated among all individuals and doses, and neither ILP100 nor CXCL12 could be detected in locations beyond the wounds. (expertsvar.se)
  • DC-SIGNR serum level was significantly increased in gastric cancer patients compared with healthy group. (biomedcentral.com)
  • Ayubi F, Ghazanfari T, Askari N, Naghizade M, Soroush M. Serum level of SDF-1α (CXCL12) in chemical victims with respiratory complications. (ijwph.ir)
  • The serum concentration of SDF-1α in SM exposed group was significantly reduced compared to the controls(p=0.046). (ijwph.ir)
  • In the present study, we demonstrated that CXCL12 rs1801157 is independently associated with HPV infection and exerts influence in HSIL development, suggesting it as a promising susceptibility biomarker for HPV infection and lesions development. (biomedcentral.com)