Abstract 389: The functional relevance of decreased ANGPTL4 in human urinary bladder cancer.

Abstract

Abstract Transitional cell carcinoma is the most common urothelial cancer in the US. Current therapeutic options have been unable to overcome issues with the highly recurrent nature of this tumor, which requires frequent follow-up making urinary bladder cancer, one of the most expensive solid tumors to manage. Microarray-based gene expression analysis in response to capsaicin treatment identified significant upregulation of angiopoietin-like 4 (ANGPTL4) compared with solvent-treated bladder cancer cells. The focus of this study was to determine the functional relevance of ANGPTL4 in normal urothelial and bladder cancer cells. The microarray data was validated in a panel of normal, immortalized and bladder cancer cells of increasing stage by real-time qPCR, immunoblotting, and ELISA. To determine the possible function of ANGPTL4, we knocked down and overexpressed ANGPTL4 in normal urothelial and bladder cancer cells respectively. The role of ANGPTL4 in growth, proliferation and angiogenesis was assessed. Our results show that normal urothelial cells have significantly higher levels of ANGPTL4 when compared to non-tumorigenic and bladder cancer cells. Upon capsaicin treatment ANGPTL4 levels increased in all cell lines tested. Overexpression of ANGPTL4 in the metastatic cell line TCCSUP, led to decrease in cell growth. Further, ANGPTL4 knockdown increased cell growth in the normal urothelial cell line. Capsaicin treatment decreased the expression of VEGF in bladder cancer cell lines UMUC-3 and T24 as well as reduced expression in normal urothelium, albeit initial results in ANGPLT4-knockdown in normal urothelium indicates no change in VEGF expression. Our results thus far suggest that the loss of ANGPTL4 expression may be involved in bladder cancer. The mechanism involved is under investigation. Capsaicin remains an attractive compound for further studies in bladder cancer. Supported by RO3 CA136058 (RG) and NIHT32 T32CA148724 (EC). Citation Format: Eduardo Cardenas, Tiffani Horton, Rita Ghosh. The functional relevance of decreased ANGPTL4 in human urinary bladder cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 389. doi:10.1158/1538-7445.AM2013-389