title: Monoclonal antibody targeting of the cell surface molecule TM4SF5 inhibits the growth of hepatocellular carcinoma.
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.
authors.affiliation: Authors' Affiliations: Center for Medical Science Research;
authors.forename: Sanghoon
authors.initials: S
authors.lastname: Kwon
authors.affiliation: Department of Pathology, College of Medicine, Hallym University, Gangwon-do;
authors.forename: Kyung-Chan
authors.initials: KC
authors.lastname: Choi
authors.affiliation: Department of Biochemistry, College of Natural Sciences, Chungbuk National University, Chungbuk; and.
authors.forename: Young-Eun
authors.initials: YE
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, College of Natural Sciences, Chungbuk National University, Chungbuk; and.
authors.forename: Yang-Wha
authors.initials: YW
authors.lastname: Ha
authors.affiliation: Authors' Affiliations: Center for Medical Science Research;
authors.forename: Dongbum
authors.initials: D
authors.lastname: Kim
authors.affiliation: Department of Microbiology, College of Medicine;
authors.forename: Byoung Kwon
authors.initials: BK
authors.lastname: Park
authors.affiliation: Authors' Affiliations: Center for Medical Science Research;
authors.forename: Guang
authors.initials: G
authors.lastname: Wu
authors.affiliation: Department of Biochemistry, College of Science, Yonsei University, Seoul, Republic of Korea.
authors.forename: Doo-Sik
authors.initials: DS
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, College of Natural Sciences, Chungbuk National University, Chungbuk, Republic of Korea. yhl4177@cbnu.ac.kr
authors.forename: Younghee
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Authors' Affiliations: Center for Medical Science Research; Department of Microbiology, College of Medicine; hjookwon@hallym.ac.kr yhl4177@cbnu.ac.kr.
authors.forename: Hyung-Joo
authors.initials: HJ
authors.lastname: Kwon
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology*; D000918:Antibody Specificity; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D015820:Cadherins / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009928:Organ Specificity; D021381:Protein Transport; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays; D020741:rho GTP-Binding Proteins / Q000378:metabolism
chemical_list: D000199:Actins; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D015820:Cadherins; D008565:Membrane Proteins; C111029:TM4SF5 protein, human; D050760:Cyclin-Dependent Kinase Inhibitor p27; D020741:rho GTP-Binding Proteins