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.
Shen
Xiaoli
X
Department of Pharmacology and Toxicology and Sealy Center for Molecular Science, University of Texas Medical Branch, 10th and Market Streets, Galveston 77555, USA.
Falzon
Miriam
M
D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D024042:Collagen Type I / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D039423:Integrin alpha1 / Q000378:metabolism; D039482:Integrin alpha5 / Q000378:metabolism; D039503:Integrin alpha6 / Q000378:metabolism; D039663:Integrin beta4 / Q000378:metabolism; D016023:Integrins / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism; D008297:Male; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D044162:Parathyroid Hormone-Related Protein / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D011471:Prostatic Neoplasms / Q000209:etiology / Q000473:pathology*; D021122:Protein Subunits / Q000378:metabolism; D014162:Transfection
D024042:Collagen Type I; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D039423:Integrin alpha1; D039482:Integrin alpha5; D039503:Integrin alpha6; D039663:Integrin beta4; D016023:Integrins; D007797:Laminin; D044162:Parathyroid Hormone-Related Protein; D021122:Protein Subunits