OSTEOPONTIN STIMULATES A SUBPOPULATION OF QUIESCENT HUMAN PROSTATE EPITHELIAL-CELLS WITH HIGH PROLIFERATIVE POTENTIAL TO DIVIDE IN-VITRO

BACKGROUND. Osteopontin (OPN) is a secreted extracellular matrix (ECM) protein found in bone, as well as associated with epithelial cells. T he main objective of these studies was to test in vitro the hypothesis that interaction with OPN stimulates proliferation of a quiescent sub population of prostate epithelial cells with high proliferative potent ial. METHODS. To simulate conditions that restrict proliferation and i nhibit terminal differentiation of basal cells in vivo, control cultur es grew on substrate coated with collagen (CO) or fibronectin (FN), in medium containing low levels of growth factors. RESULTS. Under growth -restricting conditions, most prostate epithelial cells with high prol iferative potential, seeded in control secondary cultures, were quiesc ent within the time frame of the studies, as indicated by the small nu mber of large colonies in these cultures. Growing prostate epithelial cells (PR) under the same growth-restricting conditions, bur on substr ate coated with OPN instead of CO or FN, stimulated proliferation of a subpopulation of single cells with high proliferative ability as indi cated by: 1) dose-dependent increase in the percentage of single cells incorporating bromodeoxyuridine, i.e., proliferating PR; and 2) subse quent dose-dependent increase in the percentage of large colonies. The OPN effect was not merely due to preferential attachment to OPN, beca use PR attachment to OPN, CO, or FN was identical. PR attachment to OP N was inhibited in the presence of GRGDTP or an antibody against the i ntegrin subunit alpha(v), but not in the presence of an RGES peptide o r a nonspecific IgG. CONCLUSIONS. Integrin-mediated OPN/PR interaction stimulates proliferation of a quiescent subpopulation of prostate epi thelial cells with high proliferative potential, possibly stem cells. (C) 1998 Wiley-Liss, Inc.