Vascular cell adhesion molecule-1 (VCAM-1) is closely associated with tumor progression\nand metastasis. However, the relevance and role of VCAM-1 in lung cancer have not been clearly\nelucidated. In this study, we found that VCAM-1 was highly overexpressed in lung cancer tissue\ncompared with that of normal lung tissue, and high VCAM-1 expression correlated with poor survival\nin lung cancer patients. VCAM-1 knockdown reduced migration of A549 human lung cancer cells\ninto Matrigel, and competitive blocking experiments targeting the Ig-like domain 6 of VCAM-1\n(VCAM-1-D6) demonstrated that the VCAM-1-D6 domain was critical for VCAM-1 mediated A549\ncell migration into Matrigel. Next, we developed a human monoclonal antibody specific to human\nand mouse VCAM-1-D6 (VCAM-1-D6 huMab), which was isolated from a human synthetic antibody\nlibrary using phage display technology. Finally, we showed that VCAM-1-D6 huMab had a nanomolar\naffinity for VCAM-1-D6 and that it potently suppressed the migration of A549 and NCI-H1299 lung\ncancer cell lines into Matrigel. Taken together, these results suggest that VCAM-1-D6 is a key domain\nfor regulating VCAM-1-mediated lung cancer invasion and that our newly developed VCAM-1-D6\nhuMab will be a useful tool for inhibiting VCAM-1-expressing lung cancer cell invasion.
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