title: Type I collagen-mediated proliferation of PC3 prostate carcinoma cell line: implications for enhanced growth in the bone microenvironment.
abstract: Prostate cancer is the second leading cause of male cancer-related deaths in the United States. Interestingly, prostate cancer preferentially metastasizes to bone. Once in the bone microenvironment, advanced prostate cancer becomes highly resistant to therapeutic modalities. Several factors, such as, extracelluar matrix components, have been implicated in the spread and propagation of prostatic carcinoma. The prostate cell line, PC3, adhere and spread on collagen I to a greater degree than on fibronectin (FN) or poly-L-lysine (PLL). Flow cytometry analysis reveals the presence of the alpha(1), alpha(2) and alpha(3) collagen binding integrin subunits. Antibody function blocking studies reveal that PC3 cells can utilize alpha(2)beta(1) and alpha(3)beta(1) integrins to adhere to collagen I. Cells plated on collagen I exhibit increased rates of proliferation over cells plated on FN or tissue culture plastic. Additionally, cells plated on collagen I show increased expression of cyclin D1, a molecule associated with progression through G1 phase of the cell cycle. Inhibitor studies point to a role for phosphatidylinositol 3-kinase (PI3K), map kinase (MAPK) and p70 S6 kinase in collagen I-mediated PC3 cell proliferation and cyclin D1 expression. Type I collagen may facilitate the colonization and growth of metastatic prostate tumor cells in the bone microenvironment.
authors.affiliation: Department of Biological Sciences, University of Delaware, Newark, DE 19713, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Kiefer
authors.forename: M C
authors.initials: MC
authors.lastname: Farach-Carson
mesh_terms: D001859:Bone Neoplasms / Q000378:metabolism / Q000556:secondary*; D001842:Bone and Bones / Q000378:metabolism*; D002448:Cell Adhesion; D002455:Cell Division; D024042:Collagen Type I / Q000378:metabolism*; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D024042:Collagen Type I