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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 implication of TM4SF5 and the suppressive effect of anti-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.

SUBMITTER: Park S

PROVIDER: S-EPMC6924189 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Project description:BackgroundPatients with pancreatic cancer have a poor prognosis and are usually diagnosed at a late stage. Because TM4SF5 is known to be overexpressed in hepatocellular carcinoma, colon cancer, and pancreatic cancer, it is considered as one of the candidate molecular targets for an anticancer strategies.PurposeThe purpose of this study was to evaluate possible utility of TM4SF5 to treat pancreatic cancer using a mouse allograft model.Materials and methodsWe analyzed expression of TM4SF5 in pancreatic cancer tissues using immunohistochemistry. We established a mouse pancreatic cancer cell line stably expressing TM4SF5 and identified the effect of TM4SF5 expression in vitro. We used the CpG-DNA-peptide-liposome complex as a peptide vaccine and investigated antitumor effects of the vaccine in a mouse model with TM4SF5 expressing pancreatic cells. To investigate the function of produced antibody, we evaluated effects of the anti-TM4SF5 monoclonal antibody in vitro in terms of cell growth and migration properties.ResultsImmunohistochemical analysis showed that 36.4% of pancreatic cancer tissue samples expressed TM4SF5. Expression of TM4SF5 induced increased cell proliferation and motility in vitro. Injection of the TM4SF5 peptide vaccine induced the production of anti-hTM4SF5 antibodies and reduced the growth of pancreatic tumors in mice established by subcutaneous injection of the TM4SF5-expressing mouse pancreatic cancer cell line. The treatment of TM4SF5-expressing cells with the anti-hTM4SF5 monoclonal antibody reduced cell growth, modulated the expression of the epithelial-mesenchymal transition markers Vimentin and E-cadherin, and decreased cell motility in vitro.ConclusionOur results showed that the TM4SF5 peptide vaccine had a protective effect against pancreatic tumors expressing TM4SF5, and this effect was mediated, at least in part, by the production and suppressive function of the anti-TM4SF5 antibodies. Therefore, we suggest that targeting TM4SF5 could be a novel strategy to prevent or treat pancreatic cancer.

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

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