Chondrosarcoma, a common malignant tumour, develops in bone. Effective adjuvant therapy remains inadequate for treatment, meaning poor prognosis. It is imperative to explore novel remedies. Angiogenesis is a rate-limiting step in progression that explains neovessel formation for blood supply in the tumour microenvironment. Numerous studies indicate that EPCs (endothelial progenitor cells) promote angiogenesis and contribute to tumour growth. bFGF (basic fibroblast growth factor), a secreted cytokine, regulates biological activity, including angiogenesis, and correlates with tumorigenesis. However, the role of bFGF in angiogenesis-related tumour progression by recruiting EPCs in human chondrosarcoma is rarely discussed. 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. Our in vivo data revealed that tumour-secreted bFGF promotes angiogenesis in both mouse plug and chick CAM (chorioallantoic membrane) assays. Xenograft mouse model data, due to bFGF-regulated angiogenesis, showed the bFGF regulates angiogenesis-linked tumour growth. Finally, bFGF was highly expressed in chondrosarcoma patients compared with normal cartilage, positively correlating with VEGF expression and tumour stage. The present study reveals a novel therapeutic target for chondrosarcoma progression.
Basic fibroblast growth factor induces VEGF expression in chondrosarcoma cells and subsequently promotes endothelial progenitor cell-primed angiogenesis
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Huey-En Tzeng, Po-Chun Chen, Kai-Wei Lin, Chih-Yang Lin, Chun-Hao Tsai, Shao-Min Han, Chieh-Lin Teng, Wen-Li Hwang, Shih-Wei Wang, Chih-Hsin Tang; Basic fibroblast growth factor induces VEGF expression in chondrosarcoma cells and subsequently promotes endothelial progenitor cell-primed angiogenesis. Clin Sci (Lond) 1 July 2015; 129 (2): 147–158. doi: https://doi.org/10.1042/CS20140390
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