Research Papers:

WISP-3 inhibition of miR-452 promotes VEGF-A expression in chondrosarcoma cells and induces endothelial progenitor cells angiogenesis

Chih-Yang Lin, Huey-En Tzeng, Te-Mao Li, Hsien-Te Chen, Yi Lee, Yi-Chen Yang, Shih-Wei Wang, Wei-Hung Yang and Chih-Hsin Tang _

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Oncotarget. 2017; 8:39571-39581. https://doi.org/10.18632/oncotarget.17142

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Chih-Yang Lin1,*, Huey-En Tzeng2,3,*, Te-Mao Li4, Hsien-Te Chen4,5, Yi Lee6, Yi-Chen Yang7, Shih-Wei Wang8, Wei-Hung Yang4,7,9 and Chih-Hsin Tang1,10,11

1Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan

2Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan

3Department of Internal Medicine, Division of Hematology and Oncology, Taipei Medical University Hospital, Taipei, Taiwan

4School of Chinese Medicine, China Medical University, Taichung, Taiwan

5Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan

6School of Pharmacy, China Medical University, Taichung, Taiwan

7Department of Nursing, National Taichung University of Science and Technology, Taichung, Taiwan

8Department of Medicine, Mackay Medical College, New Taipei City, Taiwan

9Department of Orthopedic Surgery, Taichung Hospital, Ministry of Health and Welfare, Taichung, Taiwan

10Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan

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

*Co-first author

Correspondence to:

Chih-Hsin Tang, email: [email protected]

Wei-Hung Yang, email: [email protected]

Keywords: WISP-3, VEGF-A, angiogenesis, miR-452

Received: October 25, 2016    Accepted: March 29, 2017    Published: April 17, 2017


Chondrosarcoma is the second most prevalent general primary tumor of bone following osteosarcoma. Chondrosarcoma development may be linked to angiogenesis, which is principally elicited by vascular endothelial growth factor-A (VEGF-A). VEGF-A level has been recognized as a prognostic marker in angiogenesis. WNT1-inducible signaling pathway protein-3 (WISP)-3/CCN6 belongs to the CCN family and is involved in regulating several cellular functions, including cell proliferation, differentiation, and migration. Nevertheless, the effect of WISP-3 on VEGF-A production and angiogenesis in human chondrosarcoma remains largely unknown. This current study shows that WISP-3 promoted VEGF-A production and induced angiogenesis of human endothelial progenitor cells. Moreover, WISP-3-enhanced VEGF-A expression and angiogenesis involved the c-Src and p38 signaling pathways, while miR-452 expression was negatively affected by WISP-3 via the c-Src and p38 pathways. Our results illustrate the clinical significance of WISP-3, VEGF-A and miR-452 in human chondrosarcoma patients. WISP-3 may illustrate a novel therapeutic target in the metastasis and angiogenesis of chondrosarcoma.

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