A large extracellular loop of TSPAN8 as a novel therapeutic target for metastatic colorectal cancer cell invasion

Abstract

We recently reported a study that identified the relevance of the large extracellular loop of tetraspanin 8 (TSPAN8-LEL) in metastatic colorectal cancer (mCRC) cell invasion. This study suggested a functional role for TSPAN8-LEL in mCRC cell invasion and the potential use of an antibody to inhibit the invasion of TSPAN8-expressing mCRCs. In this research highlight, we describe TSPAN8-LEL as a novel potential therapeutic target in mCRCs. TSPAN8 plays a key role in TSPAN8-expressing HCT116 mCRC cell invasion. Among its two extracellular loops, TSPAN8-LEL is the key domain that regulates HCT116 mCRC cell invasion. In addition, a fully human monoclonal antibody specific to TSPAN8-LEL (anti-TSPAN8-LEL HuMab) efficiently suppresses the invasion of HCT116 and LoVo mCRC cell lines more potently than HCT-8 and SW480 non-mCRC cell lines. These results indicate that targeting TSPAN8-LEL may suppress the invasion of TSPAN8-expressing mCRCs. Therefore, TSPAN8 may be a novel potential therapeutic target for antibody-based mCRC therapy.