Preprint Article Version 1 This version is not peer-reviewed

Identification of the Sixth Ig-like Domain of VCAM-1 as a Novel Therapeutic Target in Lung Cancer Cell Invasion

These authors contributed equally to this work.
Version 1 : Received: 15 February 2017 / Approved: 15 February 2017 / Online: 15 February 2017 (10:45:16 CET)

A peer-reviewed article of this Preprint also exists.

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, 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.

Journal reference: Int. J. Mol. Sci. 2017, 18, 566
DOI: 10.3390/ijms18030566

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, and high VCAM-1 expression correlated with poor survival of lung cancer patients. VCAM-1 knockdown reduced invasion in A549 human lung cancer cells, 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 invasion. 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 invasion in A549 and NCI-H1299 lung cancer cell lines. Taken together, these results suggest that VCAM-1-D6 is a novel therapeutic target in 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.

Subject Areas

human antibody; invasion; lung cancer; therapeutic target; VCAM-1; VCAM-1-D6

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