Abstract 4: WISP-1 increases angiogenesis and VEGF-A expression in human oral squamous cell carcinomas

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Oral squamous cell carcinomas (OSCC) is most common metastasis to cervical lymph nodes by angiogenesis. Wnt-1 induced secreted protein 1 (WISP-1) is a cysteine-rich protein that belongs to the CNN family (CTGF / CYR61 / NOV). However, the effects of WISP-1 on angiogenesis and Vascular endothelial growth factor- A (VEGF-A) expression in human OSCC are not clear. First, we found that the expression of WISP-1 in human OSCC tissues were higher than in normal oral tissues. We also demonstrated that WISP-1 enhanced angiogenesis and VEGF-A up-regulation in human OSCC. WISP-1 induced VEGF-A expressio and angiogenesis through αvβ3 integrin, FAK, c-Src, EGFR, and ERK pathway. Knockdown 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) and matrix gel 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. We characterized an important role for WISP-1 which regulates angiogenesis by increasing VEGF-A expression in human OSCC via the αvβ3 integrin, FAK, c-Src, EGFR, ERK, and HIF1-α signaling pathway. Citation Format: Ching-Wen Tsao, Chih-Hsin Tang, Jing-Yuan Chuang. WISP-1 increases angiogenesis and VEGF-A expression in human oral squamous cell carcinomas. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4. doi:10.1158/1538-7445.AM2014-4