SUMMARY:Malignant tumor cell invasion is determinant for metastasis to occur. E2 and C5 colon carcinoma cells that were derived from the parental Lovo line and that differ experimentally in spontaneous metastatic ability have been monitored for gene expression by cDNA arrays. Among genes found differentially expressed, the CD63 tetraspanin, not previously recognized in colon cancer progression, and the ␣3 integrin chain were both up-regulated in low metastatic E2 cells and were analyzed for their functional role using adhesion, migration, and invasion assays. Cell surface expression of CD63 and ␣3 integrin was about 2-fold higher in E2 than in C5 cells and confocal microscopy showed that CD63 and ␣3 integrin colocalized evenly on C5 cells whereas they concentrated at elongated tips of the low-metastatic more substrate-adhesive E2 cells. Antibody-interference experiments identified laminin-5 (LN-5) as a ligand interacting with the ␣31/CD63 complex. Substrate-immobilized anti-CD63 antibodies enhanced tumor cell migration and invasion and induced prominent cell surface protrusions that were repressed by the PI3-kinase LY294002 inhibitor. Our results suggest that changes in the expression of surface CD63 and ␣31 integrin interacting with LN-5 could affect migratory signals and the progression of the metastatic disease. (Lab Invest 2002, 82:1715-1724.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.