CXCL12 and Vascular Endothelial Growth Factor Synergistically Induce Neoangiogenesis in Human Ovarian Cancers

摘要: Ovarian carcinomas have a poor prognosis, often associated with multifocal i.p. dissemination accompanied by intense neovascularization. To examine tumor angiogenesis in the microenvironment, we studied malignant ascites and tumors of patients untreated ovarian carcinoma. We observed that fluid induced potent vivo neovascularization Matrigel assay. detected sizable amount vascular endothelial cell growth factor (VEGF) ascites. However, pathologic concentration VEGF is insufficient to induce angiogenesis. show strongly express CXC chemokine stromal-derived (SDF-1/CXCL12). High CXCL12, but not CXCL12 induces Strikingly, concentrations efficiently synergistically Migration, expansion, survival cells (VEC) form essential functional network further provide mechanistic basis for explaining interaction between VEGF. up-regulates receptor CXCR4 expression on VECs, synergizes CXCL12-mediated VEC migration. VEGF-mediated expansion protects VECs from sera starvation-induced apoptosis Finally, hypoxia synchronously production. Therefore, triggered synergistic angiogenic axis vivo. Hypoxia-induced signals would be important initiating maintaining an active angiogeneic pathway mediated Thus, interrupting this axis, rather than alone, will novel efficient antiangiogenesis strategy treat cancer.