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

Collection with item attached
2017
Item details URL
http://open-repository.kisti.re.kr/cube/handle/open_repository/473662.do
DOI
10.3390/ijms18030566
Title
A Human Antibody That Binds to the Sixth Ig-Like Domain of VCAM-1 BlocksLung Cancer Cell Migration In Vitro
Description
This work was supported by grants from the Scripps Korea AntibodyInstitute (10TS03), the Korean Drug Development Fund (KDDF-201210-05),and the Bio & Medical Technology Development Program of the NationalResearch Foundation (NRF) funded by the Korean government (MSIP)(2015M3A9 D9074279).
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.
provenance
Made available in Cube on 2018-09-28T10:25:34Z (GMT). No. of bitstreams: 0
language
English
author
Kim, Mi Ra
Jang, Ji Hye
Park, Chang Sik
Kim, Taek-Keun
Kim, Youn-Jae
Chung, Junho
Shim, Hyunbo
Nam, In Hyun
Han, Jung Min
Lee, Sukmook
accessioned
2018-09-28T10:25:34Z
available
2018-09-28T10:25:34Z
issued
2017
citation
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES(18): 3
issn
1422-0067
uri
http://open-repository.kisti.re.kr/cube/handle/open_repository/473662.do
Funder
교육부
Funding Program
BK21플러스사업(0.5)
Project ID
1345274070
Jurisdiction
Rep.of Korea
Project Name
Biomedical Science Project
rights
openAccess
subject
human antibody
invasion
lung cancer
Matrigel
migration
VCAM-1
VCAM-1-D6
type
article


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