Abstract
The cell surface transmembrane receptor TM4SF5 has been implicated in hepatocellular carcinoma (HCC), but its candidacy as a therapeutic target has not been evaluated. Building on findings that immunization with a peptide vaccine targeting human TM4SF5 can exert prophylactic and therapeutic effects in a murine model of HCC, we developed a monoclonal antibody to characterize expression of TM4SF5 in HCC and to target its function there as an anticancer strategy. We found that the antibody modulated cell signaling in HCC cells in vitro, reducing cell motility, modulating E-cadherin expression, altering p27(kip1) localization, and increasing RhoA activity. Using a mouse xenograft model of human HCC, we documented the in vivo efficacy of the antibody, which suppressed tumor growth in either tumor prevention or treatment designs. Our work offers a preclinical proof of concept for TM4SF5 as a promising target for antibody therapeutics to treat HCC. Cancer Res; 74(14); 3844-56. ©2014 AACR.
Highlights
Hepatocellular carcinoma (HCC) is one of the most common cancers and the second or third most frequent cause of cancer-related death worldwide [1, 2]
As previous data had shown that an anti-TM4SF5 monoclonal antibody reacted against mouse TM4SF5, we sought to explore its specificity toward the human protein
We investigated the reactivity of this anti-TM4SF5 monoclonal antibody against the human and mouse TM4SF5R2-3 peptides using enzyme-linked immunosorbent assays (ELISA), and the anti-TM4SF5 monoclonal antibody reacted with both the human and mouse TM4SF5R2-3 peptides (Supplementary Fig. S1B and S1C)
Summary
Hepatocellular carcinoma (HCC) is one of the most common cancers and the second or third most frequent cause of cancer-related death worldwide [1, 2]. HCC is the most common type of liver cancer and is usually associated with prior hepatitis virus infection or liver cirrhosis. The primary treatment for HCC is surgical resection; the high frequency of recurrence and poor liver function following the removal of liver tissue are significant obstacles to recovery [3]. HCC is frequently resistant to conventional chemotherapy and radiotherapy [4]. Understanding the signaling pathways involved in HCC development and developing targeted therapies is likely to be an important strategy for the effective treatment of HCC [3, 5]. Authors' Affiliations: 1Center for Medical Science Research; 2Department of Microbiology, College of Medicine; 3Department of Pathology, College of Medicine, Hallym University, Gangwon-do; 4Department of Biochemistry, College of Natural Sciences, Chungbuk National University, Chungbuk; and 5Department of Biochemistry, College of Science, Yonsei University, Seoul, Republic of Korea
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
