WISP-1 Increases VEGF-A Expression and Angiogenesis in Human Oral Squamous Cell Carcinomas

• Main Authors: Ching-Wen Tsao, 曹瀞文
• Other Authors: Jing-Yuan Chuang
• Format: Others
• Language: zh-TW
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/73s942

碩士 === 中國醫藥大學 === 醫學檢驗生物技術學系碩士班 === 102 === Oral squamous cell carcinomas (OSCC) is most likely metastastic to cervical lymph nodes. The formation of new blood vessels (angiogenesis) is important not only in supporting tumor growth, but also in metastasis. OSCC secretes variety of proteins inculding Wnt-1 induced secreted protein 1 (WISP-1) that belongs to the CCN family (Cyr61/ CTGF/ NOV). However, the effects of WISP-1 on angiogenesis in human OSCC are not clear. In this report, we found that WISP-1 enhanced angiogenesis and VEGF-A up-regulation in human OSCC cell line. The expression of WISP-1 in human OSCC tissue were higher than in normal oral tissues. WISP-1 induced VEGF-A expression and angiogenesis through Integrin ?庮??3 and the FAK, c-Src, EGFR, ERK and HIF1-?? signal transduction pathway. Knockdown of WISP-1 decreased VEGF-A expression and also abolished human OSCC condition medium-mediated angiogenesis in vitro as well as angiogenesis effects in the chick chorioallantoic membrane (CAM) assay and Matrigel plug nude mice model in vivo. In addition, in the xenograft tumor angiogenesis model, Knockdown of WISP-1 significantly reduced tumor growth and tumor-associated angiogenesis. These data represent, to our knowledge, the first identification that WISP-1 regulate angiogenesis by increasing VEGF-A expression in OSCC and other human cancers.