title: Generation of a human antibody that inhibits TSPAN8-mediated invasion of metastatic colorectal cancer cells.
abstract: 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.
authors.affiliation: Laboratory of Molecular Cancer Therapeutics, Scripps Korea Antibody Institute, Chuncheon, South Korea.
authors.forename: Taek-Keun
authors.initials: TK
authors.lastname: Kim
authors.affiliation: Laboratory of Molecular Cancer Therapeutics, Scripps Korea Antibody Institute, Chuncheon, South Korea.
authors.forename: Chang Sik
authors.initials: CS
authors.lastname: Park
authors.affiliation: Laboratory of Molecular Cancer Therapeutics, Scripps Korea Antibody Institute, Chuncheon, South Korea.
authors.forename: Mee Hyun
authors.initials: MH
authors.lastname: Jeoung
authors.affiliation: Laboratory of Molecular Cancer Therapeutics, Scripps Korea Antibody Institute, Chuncheon, South Korea.
authors.forename: Woo Ran
authors.initials: WR
authors.lastname: Lee
authors.affiliation: Laboratory of Molecular Cancer Therapeutics, Scripps Korea Antibody Institute, Chuncheon, South Korea.
authors.forename: Nam Kyung
authors.initials: NK
authors.lastname: Go
authors.affiliation: Laboratory of Molecular Cancer Therapeutics, Scripps Korea Antibody Institute, Chuncheon, South Korea.
authors.forename: Jong Rip
authors.initials: JR
authors.lastname: Choi
authors.affiliation: Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul, South Korea.
authors.forename: Tae Sup
authors.initials: TS
authors.lastname: Lee
authors.affiliation: Departments of Bioinspired Science and Life Science, Ewha Womans University, Seoul, South Korea.
authors.forename: Hyunbo
authors.initials: H
authors.lastname: Shim
authors.affiliation: Laboratory of Molecular Cancer Therapeutics, Scripps Korea Antibody Institute, Chuncheon, South Korea. Electronic address: lees@skai.or.kr.
authors.forename: Sukmook
authors.initials: S
authors.lastname: Lee
mesh_terms: D000911:Antibodies, Monoclonal / Q000235:genetics / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary*; D015195:Drug Design; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods; D009361:Neoplasm Invasiveness; D015202:Protein Engineering / Q000379:methods; D059470:Tetraspanins / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; C065609:TSPAN8 protein, human; D059470:Tetraspanins
keywords: Colorectal cancer cells; Human antibody; Invasion; Large extracellular loop; TSPAN8