Journal
ONCOTARGET
Volume 8, Issue 24, Pages 39571-39581Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.17142
Keywords
WISP-3; VEGF-A; angiogenesis; miR-452
Categories
Funding
- Ministry of Science and Technology of Taiwan [MOST 103-2628-B-039-002-MY3]
- China Medical University [DMR-106-079]
- Taichung Veterans General Hospital [TCVGH-NTUST1068502, TCVGH-1053701C, TCVGH:1063701C]
- Taichung Hospital, Ministry of Health and Welfare [10623]
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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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