Research Papers:

CCL5 promotes VEGF-dependent angiogenesis by down-regulating miR-200b through PI3K/Akt signaling pathway in human chondrosarcoma cells

Guan-Ting Liu, Hsien-Te Chen, Hsi-Kai Tsou, Tzu-Wei Tan, Yi-Chin Fong, Po-Chen Chen, Wei-Hung Yang, Shih-Wei Wang, Jui-Chieh Chen and Chih-Hsin Tang _

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Oncotarget. 2014; 5:10718-10731. https://doi.org/10.18632/oncotarget.2532

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Guan-Ting Liu1, Hsien-Te Chen2,3, Hsi-Kai Tsou4,5, Tzu-Wei Tan6, Yi-Chin Fong2,3, Po-Chen Chen2, Wei-Hung Yang3,7,8 , Shih-Wei Wang9, Jui-Chieh Chen10 and Chih-Hsin Tang1,6,10,11

1 Ph.D. Program for Aging, China Medical University, Taichung, Taiwan

2 Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan

3 School of Chinese Medicine, China Medical University, Taichung, Taiwan

4 Functional Neurosurgery Division, Neurological Institute, Taichung Veterans General Hospital, Taichung, Taiwan

5 Department of Early Childhood Care and Education, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli County, Taiwan

6 Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan

7 Department of Orthopedic Surgery, Taichung Hospital, Ministry of Health and Welfare, Taichung, Taiwan

8 Department of Nursing, National Taichung University of Science and Technology, Taichung, Taiwan

9 Department of Medicine, Mackay Medical College, New Taipei City, Taiwan

10 Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan

11 Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan


Chih-Hsin Tang, email:

Keywords: Angiogenesis; CCL5; Chondrosarcoma; miR-200b; VEGF

Received: July 28, 2014 Accepted: September 25, 2014 Published: September 26, 2014


Chondrosarcoma is the second most common primary malignant bone cancer, with potential for local invasion and distant metastasis. Chemokine CCL5 (formerly RANTES) of the CC-chemokine family plays a crucial role in metastasis. Angiogenesis is essential for the cancer metastasis. However, correlation of CCL5 with vascular endothelial growth factor (VEGF) expression and angiogenesis in human chondrosarcoma is still unknown. CCL5-mediated VEGF expression was assessed by qPCR, ELISA, and Western blotting. CCL5-induced angiogenesis was examined by migration and tube formation in endothelial progenitor cells in vitro. CCL5 increased VEGF expression and also promoted chondrosarcoma conditional medium-mediated angiogenesis in vitro and in vivo. Stimulation of chondrosarcoma with CCL5 augmented PI3K and Akt phosphorylation, while PI3K and Akt inhibitor or siRNA abolished CCL5-induced VEGF expression and angiogenesis. We also demonstrated CCL5 inhibiting miR-200b expression and miR-200b mimic reversing the CCL5-enhanced VEGF expression and angiogenesis. Moreover, in chondrosarcoma patients showed the positive correlation between CCL5 and VEGF; negative correlation between CCL5 and miR-200b. Taken together, results demonstrate CCL5 promoting VEGF-dependent angiogenesis in human chondrosarcoma cells by down-regulating miR-200b through PI3K/Akt signaling pathway.

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