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A Human Antibody That Binds to the Sixth Ig-Like Domain of VCAM-1 Blocks Lung Cancer Cell Migration In Vitro

Title
A Human Antibody That Binds to the Sixth Ig-Like Domain of VCAM-1 Blocks Lung Cancer Cell Migration In Vitro
Authors
Kim, Mi RaJang, Ji HyePark, Chang SikKim, Taek-KeunKim, Youn-JaeChung, JunhoShim, HyunboNam, In HyunHan, Jung MinLee, Sukmook
Ewha Authors
심현보
SCOPUS Author ID
심현보scopus
Issue Date
2017
Journal Title
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
ISSN
1422-0067JCR Link
Citation
vol. 18, no. 3
Keywords
human antibodyinvasionlung cancerMatrigelmigrationVCAM-1VCAM-1-D6
Publisher
MDPI AG
Indexed
SCIE; SCOPUS WOS scopus
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.
DOI
10.3390/ijms18030566
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일반대학원 > 바이오융합과학과 > Journal papers
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