PTH-related protein modulates PC-3 prostate cancer cell adhesion and integrin subunit profile

Parathyroid hormone-related protein (PTHrP), which has been localized in prostate cancer tissue and cell lines, plays a role in the development of bone metastases, a frequent complication in prostate cancer patients. Tumor cell adhesion to extracellular matrix (ECM) components is mediated via integrin subunits, and plays a major role in the invasion and metastasis of tumor cells. The present experiments examined the ability of PTHrP to influence adhesion of the human prostate cancer cell line PC-3 to several ECM proteins found in normal tissues. Clonal PC-3 cells induced to overexpress PTHrP by stable transfection with PTHrP complementary DNA showed significantly higher adhesion to collagen type 1, fibronectin, and laminin than control (empty vector-transfected) cells. PTHrP-overexpressing cells also exhibited higher expression of the alpha1, alpha5, alpha6, and beta4 integrin subunits. These results suggest that PTHrP may play a role in prostate tumor invasion and metastasis by influencing cell adhesion to the ECM via upregulation of specific integrin subunits.