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Therapeutic effect of a TM4SF5-specific monoclonal antibody against colon cancer in a mouse model

2014; Impact Journals LLC; Volume: 5; Issue: 18 Linguagem: Inglês

10.18632/oncotarget.2311

1949-2553

Young-Eun Kim, Sanghoon Kwon, Guang Wu, Dongbum Kim, Byoung Kwon Park, Jeong-A Park, Kyung‐Chan Choi, Doo‐Sik Kim, Hyung‐Joo Kwon, Younghee Lee,

Cell Adhesion Molecules Research

// Young-Eun Kim 1,* , Sanghoon Kwon 2,* , Guang Wu 2,* , Dongbum Kim 2 , Byoung Kwon Park 3 Jeong-A Park 1 , Kyung-Chan Choi 4 , Doo-Sik Kim 5 , Hyung-Joo Kwon 2,3 and Younghee Lee 1 1 Department of Biochemistry, College of Natural Sciences, Chungbuk National University, Chungbuk, Republic of Korea 2 Center for Medical Science Research, College of Medicine, Hallym University, Gangwon-do, Republic of Korea 3 Department of Microbiology, College of Medicine, Hallym University, Gangwon-do, Republic of Korea 4 Department of Pathology, College of Medicine, Hallym University, Gangwon-do, Republic of Korea 5 Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea * These authors contributed equally to this work Correspondence: Kwon HJ, email: // Younghee Lee, email: // Keywords : TM4SF5, monoclonal antibody, colon cancer, therapeutics, animal model Received : June 27, 2014 Accepted : August 03, 2014 Published : August 04, 2014 Abstract Transmembrane 4 superfamily member 5 protein (TM4SF5) is presumed to serve as a molecular target to prevent or treat hepatocellular carcinoma (HCC) and colon cancer in a mouse model. Previously, we reported the efficacy of anti-cancer peptide vaccine targeting TM4SF5. In addition, we reported an anti-proliferative effect of anti-TM4SF5 monoclonal antibody in HCC. Here, we investigated expression of TM4SF5 in 45 primary colon cancer tissues. Almost all of the colon cancer tissues expressed TM4SF5 based on immunohistochemistry using anti-TM4SF5 monoclonal antibody. The treatment of human colon cancer cells with anti-TM4SF5 antibody reduced growth of TM4SF5 expressing cells and enhanced expression of E-cadherin and β-catenin. Using mouse colon cancer models, we then evaluated the in vivo anti-cancer effect of anti-TM4SF5 antibody. Injection of the antibody significantly reduced growth of tumors priorly established by subcutaneous injection of human colon cancer cells HT-29 in a xenograft setting. We obtained similar results with mouse colon cancer cell line CT-26 in an allograft setting. Therefore, we suggest that the TM4SF5-specific monoclonal antibody has a therapeutic effect against colon cancer.