Abstract 2361: The role of thrombomodulin in bladder cancer

Abstract

Abstract Bladder cancer is one of the most common cancers in the United States and Taiwan. We have discovered that thrombomodulin (TM) is up-regulated in bladder cancer patients and cancer cell lines but not in normal cells. TM is an exclusive endothelial cell surface glycoprotein and an important vascular protective molecule that has anticoagulant, anti-inflammatory and anti-apoptotic properties. TM immunohistochemical analysis of tissue microarray from bladder cancer patients of the United States was performed, and we found that TM staining was more pronounced in high grade and muscle invasive cancers. TM expression by western blot have been examined in 10 bladder cancer tissues from Taiwan in comparison to 3 normal bladder tissues, 80% (8/10) of the cancer group were over-expressed while none showed in normal bladder tissues. In a cell model, we knocked down the TM expression in BFTC905 bladder cancer cells (which was a cell line from invasive TCC) by siRNA. The two stable TM knocked-down cells (C6 and E2) showed a lower proliferation rate than BFTC905 wild type cells and vector control cells (D3). TM knocked-down cells (C6 and E2) also had lower migration and invasion abilities than control cells. Furthermore, TM knocked-down cells have a decreased colony number and size in tumor formation assays. By contrast, SV-HUC-1(immortalized human normal urothelial cell line) enhanced the migration and invasion ability by transient over-expression with TM plasmid. In an animal model, the RT-PCR analysis of the ascites from mice with peritoneal inoculation of MBT-2 cells (mouse bladder tumor cell line), we found that TM expression has higher in the group with tumor formation than the group without. These findings suggest that TM may be involved in the tumor progression of bladder cancer. Thus TM could be a bladder cancer prognosis biomarker and also be a therapeutic target. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2361. doi:10.1158/1538-7445.AM2011-2361