Vascular endothelial growth factor expression as a biomarker of prognosis in patients with chondrosarcoma, Ewing's sarcoma and osteosarcoma. Current concepts.
Survival pathways such as PI3K, AKT, mTOR and VEGF have been shown to be involved in proliferation of chondrosarcoma cells and antiapoptotic proteins may also play a relevant role.
We have developed a model of human chondrosarcoma MCTS that combines an ECM rich in glycosaminoglycans with a high hypoxic core associated with VEGF excretion.
In the present study, we found that bFGF induced VEGF (vascular endothelial growth factor) expression via the FGFR1 (fibroblast growth factor receptor 1)/c-Src/p38/NF-κB (nuclear factor κB) signalling pathway in chondrosarcoma cells, thereby triggering angiogenesis of endothelial progenitor cells.
In this study, CCL5 increased VEGF expression and also promoted chondrosarcoma medium-mediated angiogenesis in vitro as well as angiogenesis effects in the chick chorioallantoic membrane and Matrigel plug nude mice model in vivo.
Our purposes were (1) to determine if there is hypoxia-regulated microRNA overexpressed in chondrosarcoma; (2) if that contributes to increased VEGF expression; and (3) can VEGF expression be inhibited with a specific antagomir?
Knockdown of ET-1 decreased VEGF expression and also abolished chondrosarcoma conditional medium-mediated angiogenesis in vitro as well as angiogenesis effects in the chick chorioallantoic membrane and Matrigel plug nude mice model in vivo.
CXCR4 expression, analyzed by real-time PCR and Western blot, was increased in human chondrosarcoma cell line JJ compared with normal chondrocytes and was further increased in JJ by hypoxia (2% O2), vascular endothelial growth factor A (VEGFA; 10 ng/mL), and in xenograft tumors in nude mice.
We believe that IL-1beta has a stronger impact on vascularization in chondrosarcomas than hypoxia, as both factors, ADAMTS1 and VEGF-A, are regulated in a way that favors angiogenesis.
Higher VEGF-A expression levels were detected in conventional chondrosarcomas Grades II and III (using a 3-tier grading system) than in dedifferentiated chondrosarcomas (P < .05).
The role of the HIF-1alpha/VEGF pathway in angiogenesis in chondrosarcoma in vivo and its usefulness as a target for antiangiogenic treatment strategies for this tumor requires further investigation.