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

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.

• Authors: 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
• Journal: Oncotarget (Oncotarget) Vol. 5 Issue 18 Pg. 8402-15 (Sep 30 2014) ISSN: 1949-2553 [Electronic] United States
• PMID: 25268742 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antigens, CD
• Antineoplastic Agents
• CDH1 protein, human
• CTNNB1 protein, human
• Cadherins
• Membrane Proteins
• TM4SF5 protein, human
• TM4SF5 protein, mouse
• beta Catenin

Topics

• Adult
• Aged
• Animals
• Antibodies, Monoclonal (pharmacology)
• Antigens, CD
• Antineoplastic Agents (pharmacology)
• Cadherins (metabolism)
• Cell Proliferation (drug effects)
• Colorectal Neoplasms (drug therapy, immunology, metabolism, pathology)
• Female
• HCT116 Cells
• HT29 Cells
• Humans
• Male
• Membrane Proteins (antagonists & inhibitors, immunology, metabolism)
• Mice, Inbred BALB C
• Mice, Nude
• Middle Aged
• Time Factors
• Tumor Burden (drug effects)
• Xenograft Model Antitumor Assays
• beta Catenin (metabolism)