Targeting TM4SF5 with anti-TM4SF5 monoclonal antibody suppresses the growth and motility of human pancreatic cancer cells

Abstract

Pancreatic cancer is one of the most lethal cancers. Transmembrane 4 superfamily member 5 protein (TM4SF5) is one of the candidate molecular targets used for the prevention and treatment of TM4SF5-expressing cancers, including hepatocellular carcinoma, colon cancer and pancreatic cancer. Recently, a previous study reported the preventive effects of a peptide vaccine, which targeted TM4SF5, in a mouse pancreatic cancer model. The present study investigated the implicationofTM4SF5andthesuppressiveeffectofanti-human TM4SF5 monoclonal antibody (anti-hTM4SF5 antibody) in human pancreatic cancer cell lines in vitro. Treatment with anti-hTM4SF5 antibody reduced cell viability, modulated the expression of EMT markers Vimentin and E-cadherin, and decreased cell motility in human pancreatic cancer cells that endogenously expressed TM4SF5. When TM4SF5 was exogenously overexpressed in the TM4SF5-negative cell line, the cells indicated increased cell viability and motility compared with control cells, and the phenotype was reversed by anti-hTM4SF5 antibody treatment. Therefore, the results of the current study demonstrated that the high expression of TM4SF5 is a tumorigenic factor in human pancreatic cells and anti-hTM4SF5 antibody treatment exhibits a suppressive effect in TM4SF5-expressing pancreatic cancer cells.