A Human Antibody That Binds to the Sixth Ig-Like Domain of VCAM-1 Blocks Lung Cancer Cell Migration In Vitro
AbstractVascular 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. View Full-Text
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Kim, M.R.; Jang, J.H.; Park, C.S.; Kim, T.-K.; Kim, Y.-J.; Chung, J.; Shim, H.; Nam, I.H.; Han, J.M.; Lee, S. A Human Antibody That Binds to the Sixth Ig-Like Domain of VCAM-1 Blocks Lung Cancer Cell Migration In Vitro. Int. J. Mol. Sci. 2017, 18, 566.
Kim MR, Jang JH, Park CS, Kim T-K, Kim Y-J, Chung J, Shim H, Nam IH, Han JM, Lee S. A Human Antibody That Binds to the Sixth Ig-Like Domain of VCAM-1 Blocks Lung Cancer Cell Migration In Vitro. International Journal of Molecular Sciences. 2017; 18(3):566.Chicago/Turabian Style
Kim, Mi R.; Jang, Ji H.; Park, Chang S.; Kim, Taek-Keun; Kim, Youn-Jae; Chung, Junho; Shim, Hyunbo; Nam, In H.; Han, Jung M.; Lee, Sukmook. 2017. "A Human Antibody That Binds to the Sixth Ig-Like Domain of VCAM-1 Blocks Lung Cancer Cell Migration In Vitro." Int. J. Mol. Sci. 18, no. 3: 566.
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