Type I collagen-mediated proliferation of PC3 prostate carcinoma cell line: implications for enhanced growth in the bone microenvironment

Prostate cancer is the second leading cause of male cancer-related deaths i n the United States. Interestingly, prostate cancer preferentially metastas izes to bone. Once in the bone microenvironment, advanced prostate cancer b ecomes highly resistant to therapeutic modalities. Several factors, such as , extracellular matrix components, have been implicated in the spread and p ropagation 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 fun ction 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 co llagen I exhibit increased rates of proliferation over cells plated on FN o r tissue culture plastic. Additionally, cells plated on collagen I show inc reased expression of cyclin DI, a molecule associated with progression thro ugh G1 phase of the cell cycle. Inhibitor studies point to a role for phosp hatidylinositol 3-kinase (PI3K), map kinase (MAPK) and p70 S6 kinase in col lagen I-mediated PC3 cell proliferation and cyclin D1 expression. Type I co llagen may facilitate the colonization and growth of metastatic prostate tu mor cells in the bone microenvironment. (C) 2001 Elsevier Science B.V./Inte rnational Society of Matrix Biology. All rights reserved.