title: A Human Antibody That Binds to the Sixth Ig-Like Domain of VCAM-1 Blocks Lung Cancer Cell Migration In Vitro.
abstract: Vascular cell adhesion molecule-1 (VCAM-1) is closely associated with tumor progression and metastasis. However, the relevance and role of VCAM-1 in lung cancer have not been clearly elucidated. In this study, we found that VCAM-1 was highly overexpressed in lung cancer tissue compared with that of normal lung tissue, and high VCAM-1 expression correlated with poor survival in lung cancer patients. VCAM-1 knockdown reduced migration of A549 human lung cancer cells into Matrigel, and competitive blocking experiments targeting the Ig-like domain 6 of VCAM-1 (VCAM-1-D6) demonstrated that the VCAM-1-D6 domain was critical for VCAM-1 mediated A549 cell migration into Matrigel. Next, we developed a human monoclonal antibody specific to human and mouse VCAM-1-D6 (VCAM-1-D6 huMab), which was isolated from a human synthetic antibody library using phage display technology. Finally, we showed that VCAM-1-D6 huMab had a nanomolar affinity for VCAM-1-D6 and that it potently suppressed the migration of A549 and NCI-H1299 lung cancer cell lines into Matrigel. Taken together, these results suggest that VCAM-1-D6 is a key domain for regulating VCAM-1-mediated lung cancer invasion and that our newly developed VCAM-1-D6 huMab will be a useful tool for inhibiting VCAM-1-expressing lung cancer cell invasion.
authors.affiliation: Research Center, Scripps Korea Antibody Institute, Chuncheon 24341, Korea. cslove526@skai.or.kr.
authors.forename: Mi Ra
authors.initials: MR
authors.lastname: Kim
authors.affiliation: Research Center, Scripps Korea Antibody Institute, Chuncheon 24341, Korea. jjh717@skai.or.kr.
authors.forename: Ji Hye
authors.initials: JH
authors.lastname: Jang
authors.affiliation: Research Center, Scripps Korea Antibody Institute, Chuncheon 24341, Korea. pcs@skai.or.kr.
authors.forename: Chang Sik
authors.initials: CS
authors.lastname: Park
authors.affiliation: Research Center, Scripps Korea Antibody Institute, Chuncheon 24341, Korea. tkkim@skai.or.kr.
authors.forename: Taek-Keun
authors.initials: TK
authors.lastname: Kim
authors.affiliation: Specific Organs Cancer Branch, Research Institute, National Cancer Center, Goyang 10408, Korea. yjkim76@gmail.com.
authors.forename: Youn-Jae
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Biochemistry and Molecular Biology, Seoul National University, Seoul 03087, Korea. junhochung@icloud.com.
authors.forename: Junho
authors.initials: J
authors.lastname: Chung
authors.affiliation: Departments of Bioinspired Science and Life Science, Ewha Womans University, Seoul 03760, Korea. hshim@ewha.ac.kr.
authors.forename: Hyunbo
authors.initials: H
authors.lastname: Shim
authors.affiliation: Geologic Environment Division, Korea Institute of Geoscience and Mineral Resources (KIGAM), Daejeon 34132, Korea. nih@kigam.re.kr.
authors.forename: In Hyun
authors.initials: IH
authors.lastname: Nam
authors.affiliation: Department of Integrated OMICS for Biomedical Science, College of Pharmacy, Yonsei University, Incheon 21983, Korea. jhan74@yonsei.ac.kr.
authors.forename: Jung Min
authors.initials: JM
authors.lastname: Han
authors.affiliation: Research Center, Scripps Korea Antibody Institute, Chuncheon 24341, Korea. Lees@skai.or.kr.
authors.forename: Sukmook
authors.initials: S
authors.lastname: Lee
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology; D001665:Binding Sites; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D051379:Mice; D019010:Vascular Cell Adhesion Molecule-1 / Q000737:chemistry / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D019010:Vascular Cell Adhesion Molecule-1
keywords: Matrigel; VCAM-1; VCAM-1-D6; human antibody; invasion; lung cancer; migration