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

Biochem Biophys Res Commun. 2015 Dec 25;468(4):774-80. doi: 10.1016/j.bbrc.2015.11.031. Epub 2015 Nov 10.

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.

Keywords: Colorectal cancer cells; Human antibody; Invasion; Large extracellular loop; TSPAN8.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / genetics
  • Antibodies, Monoclonal / therapeutic use*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / secondary*
  • Drug Design
  • Humans
  • Molecular Targeted Therapy / methods
  • Neoplasm Invasiveness
  • Protein Engineering / methods
  • Tetraspanins / antagonists & inhibitors*
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • TSPAN8 protein, human
  • Tetraspanins