TM4SF1 Is Highly Expressed And Plays An Important Role In Pancreatic Cancer

The current study investigated TM4SF1 as a potential regulator of pancreatic cancer cell function. TM4SF1 was highly expressed in the neoplastic epithelium of human pancreatic adenocarcinomas (PDAC) analyzed by immunohistochemistry and quantitative reverse transcription-PCR (qRT-PCR). TM4SF1 mRNA expression was also found to be elevated in most pancreatic cancer cell lines compared with Human pancreatic duct epithelial (HPDE) cells. The migration and invasion of pancreatic cancer cell lines MPanc96, MIA PaCa-2, PANC-1 and HP AC were significantly decreased when TM4SF1 was silenced by either siRNA or shRNA in comparison with their respective controls. In contrast, TM4SF1 silencing had no effect on cell proliferation. Flow cytometry data showed that the gemcitabine mediated apoptosis percentage of MPanc96, MIA PaCa-2, PANC-1 and HP AC cells was significantly increased after silencing TM4SF1 in comparison with its respective controls. In vivo, silencing of TM4SF1 in MIA PaCa2 cells decreased the metastasis in lung and liver and increased the effectiveness of gemcitabine treatments in orthotopic tumor models evaluated by noninvasive bioluminescence imaging. The tube formation of HUVEC was significantly decreased after silencing of TM4SF1. In summary, these findings suggest that TM4SF1 is a surface membrane antigen expressed highly in pancreatic cancer and promotes migration, invasion and survival of the pancreatic cancer cells. Silencing of TM4SF1 reduced the tumor angiogenesis in vitro. Thus, TM4SF1 may be a useful target for future development of novel therapies for this disease.