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.
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Research Article|
April 24 2015
Basic fibroblast growth factor induces VEGF expression in chondrosarcoma cells and subsequently promotes endothelial progenitor cell-primed angiogenesis
Huey-En Tzeng;
Huey-En Tzeng
1
*Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan
†Division of Hematology/Oncology, Taichung Veterans General Hospital, Taichung, Taiwan
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Po-Chun Chen;
Po-Chun Chen
1
‡Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan
§Department of Medical Research, Chung Shan Medical University Hospital, Chung Shan Medical University, Taichung, Taiwan
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Kai-Wei Lin;
Kai-Wei Lin
‡Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan
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Chih-Yang Lin;
Chih-Yang Lin
‡Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan
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Chun-Hao Tsai;
Chun-Hao Tsai
║Department of Medicine and Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan
¶Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan
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Shao-Min Han;
Shao-Min Han
**Division of Hematology/Oncology, Department of Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
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Chieh-Lin Teng;
Chieh-Lin Teng
**Division of Hematology/Oncology, Department of Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
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Wen-Li Hwang;
Wen-Li Hwang
**Division of Hematology/Oncology, Department of Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
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Shih-Wei Wang;
Shih-Wei Wang
††Department of Medicine, Mackay Medical College, New Taipei City, Taiwan
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Chih-Hsin Tang
‡Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan
‡‡Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan
§§Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan
Correspondence: Chih-Hsin Tang (email [email protected]).
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Publisher: Portland Press Ltd
Received:
June 26 2014
Revision Received:
February 25 2015
Accepted:
March 04 2015
Accepted Manuscript online:
March 04 2015
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2015 Biochemical Society
2015
Clin Sci (Lond) (2015) 129 (2): 147–158.
Article history
Received:
June 26 2014
Revision Received:
February 25 2015
Accepted:
March 04 2015
Accepted Manuscript online:
March 04 2015
Citation
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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