Role of I-TAC-binding receptors CXCR3 and CXCR7 in proliferation, activation of intracellular signaling pathways and migration of various tumor cell lines.

Abstract

Chemokines and its receptors stimulate tumor growth, migration and invasion. In this study we evaluated the expression and function of CXCR3 and CXCR7 receptors in cervical carcinoma, rhabdomyosarcoma and glioblastoma cell lines. We found that both receptors were expressed at different degree by tumor cells. CXCR7 was expressed at both mRNA and protein level by all tumor cell lines. The expression of CXCR7 differed between rhabdomyosarcoma subtypes. The receptor was highly expressed in alveolar rhabdomyosarcoma and the expression was low in embryonal rhabdomyosarcoma. The expression of CXCR3 was low in majority of the tumor cell lines. Upon I-TAC stimulation AKT and MAPK kinases were activated. However, the activation of growth promoting pathways did not increased the proliferation rate of tumor cells. Since chemokines stimulate the migration of various cell types the ability of I-TAC to stimulate migration of tumor cells were studied. We did not observe the migration of tumor cells toward I-TAC gradient alone. However, at the low dose, I-TAC sensitized tumor cells toward SDF-1β gradient and synergized with SDF-1β in activation of intracellular pathways. Our data suggest an important role of I-TAC and its receptors in biology of solid tumors and we postulate that I-TAC-binding receptors might be used as the potential targets for antitumor therapy.

17AEP-GA, an HSP90 antagonist, is a potent inhibitor of glioblastoma cell proliferation, survival, migration and invasion

“…Similar results have been obtained for different tumors (19,22,23,28). GAs are able to inhibit the expression of MAPK and AKT kinases which were shown previously to be involved in activating the motility of tumor cells (26,27). Thus, parallel blocking of MET receptor expression and activation of kinases involved in cell migration by GAs could be responsible for observed inhibition of GBM migration and invasion after HGF stimulation.…”

“…In this study, using real-time RT-PCR and flow cytometry, we showed that GBM cells express the MET receptor and that HGF stimulates the phosphorylation of MAPK and AKT kinases in GBM cells, two kinases involved not only in tumor growth but also in tumor cell migration (26,27). Moreover, we have shown that GAs can downregulate the surface expression on MET receptor.…”

CXCL12 mediates apoptosis resistance in rat C6 glioma cells

“…However, recent investigations have shown that CXCR7 can signal via β-arrestin (30) resulting for example in CXCL12-dependent activation of MAP-kinase in interneurons in vivo (31), and MAP-kinase and Akt pathways in primary rat astrocytes and Schwann cells (14) and human glioblastoma cell lines (16). Furthermore, the second ligand for CXCR7, CXCL11 can also induce activation of MAP-kinase and Akt signaling pathways (32) and has chemotactic properties on vascular smooth muscle cells (30). Examples of the reported effects of CXCL12 via CXCR7 are chemotaxis in T lymphocytes (12), angiogenesis and invasion in hepatocellular carcinomas, while metastasis .…”

Fenofibrate attenuates contact-stimulated cell motility and gap junctional coupling in DU-145 human prostate cancer cell populations

“…DU-145 cells cultured at a density of 900 cells/mm 2 in DMEM-F12 HAM supplemented with 10% FbS for 24 h were treated with the medium containing 100 µM fenofibrate or 100 µM perhydrol (positive control) in the presence of fluorescence ROS indicator DHR 123 (dihydorhodamine 123; 1:500, Sigma) for 4 h. Measurements of DHR 123 fluorescence intensity were carried out using a bD FACSCanto™ cytometer, and the data were analyzed using the winMDI 2.8 program (29). A total of 10 5 cells was analyzed for each series.…”