Syndecan-2, a transmembrane heparan Sulfate proteoglycan, is known to serve as an adhesion receptor, but details of the regulatory mechanism governing syndecan-2 cell adhesion and migration remain unclear. Here, we examined this regulatory mechanism, showing that overexpression of syndecan-2 enhanced collagen adhesion, cell migration and invasion of normal rat intestinal epithelial cells (RIE1), and increased integrin of alpha 2 expression levels. Interestingly, RIE1 cells transfected with either syndecan-2 or integrin of alpha 2 showed similar adhesion and migration patterns, and a function-blocking anti-integrin alpha 2 antibody abolished syndecan-2-mediated adhesion and migration. Consistent with these findings, transfection of integrin alpha 2 siRNA diminished syndecan-2-induced cell migration in HCT116 human colon cancer cells. Taken together. these results demonstrate a novel cooperation between syndecan-2 and integrin alpha 2 beta 1 in adhesion-mediated cell migration and invasion. This interactive dynamic might be a possible mechanism Underlying the tumorigenic activities of colon cancer cells. (C) 2009 Elsevier Inc. All rights reserved.