Generation of a human antibody that inhibits TSPAN8-mediated invasion of metastatic colorectal cancer cells

Taek Keun Kim, Chang Sik Park, Mee Hyun Jeoung, Woo Ran Lee, Nam Kyung Go, Jong Rip Choi, Tae Sup Lee, Hyunbo Shim, Sukmook Lee

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

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.

Original languageEnglish
Pages (from-to)774-780
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume468
Issue number4
DOIs
StatePublished - 25 Dec 2015

Keywords

  • Colorectal cancer cells
  • Human antibody
  • Invasion
  • Large extracellular loop
  • TSPAN8

Fingerprint

Dive into the research topics of 'Generation of a human antibody that inhibits TSPAN8-mediated invasion of metastatic colorectal cancer cells'. Together they form a unique fingerprint.

Cite this