Basic fibroblast growth factor induces VEGF expression in chondrosarcoma cells and subsequently promotes endothelial progenitor cell-primed angiogenesis.
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.
*Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.
Huey-En
HE
Tzeng
‡Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.
Po-Chun
PC
Chen
‡Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.
Kai-Wei
KW
Lin
‡Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.
Chih-Yang
CY
Lin
║Department of Medicine and Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.
Chun-Hao
CH
Tsai
**Division of Hematology/Oncology, Department of Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
Shao-Min
SM
Han
**Division of Hematology/Oncology, Department of Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
Chieh-Lin
CL
Teng
**Division of Hematology/Oncology, Department of Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
Wen-Li
WL
Hwang
††Department of Medicine, Mackay Medical College, New Taipei City, Taiwan.
Shih-Wei
SW
Wang
‡Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.
Chih-Hsin
CH
Tang
D000818:Animals; D001859:Bone Neoplasms / Q000098:blood supply* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002642:Chick Embryo; D002813:Chondrosarcoma / Q000098:blood supply* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D049033:Chorioallantoic Membrane / Q000098:blood supply*; D004305:Dose-Response Relationship, Drug; D066026:Endothelial Progenitor Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D008297:Male; D008819:Mice, Nude; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic; D018919:Neovascularization, Physiologic; D019899:Paracrine Communication / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034622:RNA Interference; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D047368:Tumor Burden; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1; D019061:src-Family Kinases; D048051:p38 Mitogen-Activated Protein Kinases