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

• Published in: Molecular and cellular endocrinology Vol. 199; no. 1; pp. 165 - 177
• Main Authors: Shen, Xiaoli, Falzon, Miriam
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 31.01.2003
• Subjects: Cell Adhesion - drug effects; Cell Line, Tumor; Collagen Type I - metabolism; Extracellular matrix; Extracellular Matrix Proteins - metabolism; Fibronectins - metabolism; Humans; Integrin alpha1 - metabolism; Integrin alpha5 - metabolism; Integrin alpha6 - metabolism; Integrin beta4 - metabolism; Integrins; Integrins - metabolism; Laminin - metabolism; Male; Neoplasm Invasiveness; Neoplasm Metastasis; Parathyroid hormone-related protein; Parathyroid Hormone-Related Protein - genetics; Parathyroid Hormone-Related Protein - pharmacology; Parathyroid Hormone-Related Protein - physiology; PC-3 (prostate cancer cells); Prostatic Neoplasms - etiology; Prostatic Neoplasms - pathology; Protein Subunits - metabolism; Transfection; Extracellular matrix; PC-3 (prostate cancer cells); Parathyroid hormone-related protein; Integrins
• ISSN: 0303-7207; 1872-8057
• DOI: 10.1016/S0303-7207(02)00287-3

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 α1, α5, α6, and β4 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.