The class 3 semaphorins, sema3A and sema3C, provide important guidance cues in cell development and in cancer; however, the role of these semaphorins in prostate cancer is not known. We report here that sema3A transfected cells exhibit decreased invasion and adhesion in Matrigel-based assays and that sema3C transfected cells exhibit increased invasive and adhesive characteristics. Important adhesion proteins were differentially modulated in sema3A and sema3C cells in a manner consistent with their subsequent invasive and adhesive characteristics. E-cadherin expression as determined by Western blot analysis was strongly upregulated in sema3A transfected cells, but strongly downregulated in sema3C transfected cells compared to untransfected and mock empty vector-transfected PC-3 cells. β-catenin levels were not changed in sema3A transfected cells; however, sema3C transfected cells had lower expression of this protein. Sema3C transfected cells exhibited greater cellular membrane expression of certain α integrins as compared to untransfected and sema3A transfected cells, a characteristic associated with increased adhesion and invasion. These data indicate that the invasive ability of sema3A and sema3C transfected PC-3 cells is, in part, correlated with adhesion protein expression and adhesive ability to constituents of neighboring cells and the extracellular matrix.