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Generation of a human antibody that inhibits TSPAN8-mediated invasion of metastatic colorectal cancer cells
- Generation of a human antibody that inhibits TSPAN8-mediated invasion of metastatic colorectal cancer cells
- Kim, Taek-Keun; Park, Chang Sik; Jeoung, Mee Hyun; Lee, Woo Ran; Go, Nam Kyung; Choi, Jong Rip; Lee, Tae Sup; Shim, Hyunbo; Lee, Sukmook
- Ewha Authors
- SCOPUS Author ID
- Issue Date
- Journal Title
- BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
- 0006-291X; 1090-2104
- vol. 468, no. 4, pp. 774 - 780
- TSPAN8; Large extracellular loop; Human antibody; Colorectal cancer cells; Invasion
- ACADEMIC PRESS INC ELSEVIER SCIENCE
- SCI; SCIE; SCOPUS
- 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. (C) 2015 Elsevier Inc. All rights reserved.
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