Syndecan-2 expression in colorectal cancer-derived HT-29 M6 epithelial cells induces a migratory phenotype

Members of the heparan sulfate proteoglycan family, the syndecans have emer ged as integrators of extracellular signals, such as ECM components or grow th factors, that activate cytoplasmic signaling cascades and regulate cytos keletal functions. Specifically, syndecan-2 has been implicated in various cellular processes, from differentiation to migration, including its partic ipation in cell-cell and cell-matrix adhesion. Here, we focused on the invo lvement of syndecan-2 in epithelial versus mesenchymal differentiation. Col orectal cancer-derived HT-29 M6 epithelial cells were stably transfected wi th full-length syndecan-2 cDNA, and the effect on cell morphology, adhesion , and mobility was evaluated. Characteristic features of migratory cells su ch as loss of intercellular contacts, flatter shape and multiple membrane p rojections were observed in syndecan-2 transfectants. Western blot analysis of the major component of epithelial adherens junctions, E-cadherin, revea led decreased expression levels. Furthermore, syndecan-2 induced stronger a dhesion to collagen type I, specifically inhibited by heparin. This was cor related with an increased ability for migration, as demonstrated by wound h ealing experiments and transwell assays, without affecting their growth rat e. These results indicate that syndecan-2 expression in mucus-secreting HT- 29 M6 cells induces differentiation toward a migratory mesenchymal-like phe notype. (C) 2001 Academic Press.