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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
Biochemical and biophysical research communications 2015 v.468 pp. 774-780
antigens, humans, antibodies, bacteriophages, metastasis, amino acids, neoplasm cells, colorectal neoplasms
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.