Generation of a human antibody that inhibits TSPAN8-mediated invasion of metastatic colorectal cancer cells
- 주제(키워드) Colorectal cancer cells , Human antibody , Invasion , Large extracellular loop , TSPAN8
- 등재 SCIE, SCOPUS
- 발행기관 Academic Press Inc.
- 발행년도 2015
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000121368
- 본문언어 영어
- Published As http://dx.doi.org/10.1016/j.bbrc.2015.11.031
- 저작권 이화여자대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
Tetraspanin 8 (TSPAN8) is a tumor-associated antigen implicated in tumor progression and metastasis. However, the validation of TSPAN8 as a potential therapeutic target in metastatic colorectal cancer (mCRC) has not yet been studied. In this study, through several in vitro methodologies, we identified a large extracellular loop of TSPAN8 (TSPAN8-LEL) as a key domain for regulating mCRC invasion. Using phage display technology, we developed a novel anti-TSPAN8-LEL human antibody with subnanomolar affinity that specifically recognizes amino acids 140-205 of TSPAN8-LEL in a conformation-dependent manner. Finally, we demonstrated that the antibody specifically reduces invasion in the HCT116 and LoVo mCRC cell lines more potently than in the HCT-8 and SW480 non-mCRC cell lines. Our data suggest that TSPAN8-LEL may play an important role in mCRC cell invasion, and that the antibody we have developed could be a useful tool for inhibiting the invasion of TSPAN8-expressing mCRCs. © 2015 Elsevier Inc. All rights reserved.
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