title: Diminished expression of h2-calponin in prostate cancer cells promotes cell proliferation, migration and the dependence of cell adhesion on substrate stiffness.
abstract: Calponin is an actin filament-associated protein and its h2 isoform inhibits cell motility. Here we report significant expression of h2-calponin in prostate epithelial cells, which is diminished in cancerous cells. Comparison between a prostate cancer cell line PC3 and its metastatic derivative PC3-M showed lower levels of h2-calponin in PC3-M, corresponding to faster rates of cell proliferation and migration. Substrate adhesion of PC3 and PC3-M cells was positively correlated to the level of h2-calponin and the adhesion of PC3-M exhibited a higher dependence on substrate stiffness. Such effects of h2-calponin on cell proliferation, migration and substrate adhesion were also seen in normal versus cancerous primary prostate cells. Further supporting the role of h2-calponin in inhibiting cell motility, fibroblasts isolated from h2-calponin knockout mice proliferated and migrated faster than that of wild type fibroblasts. Transfective over-expression of h2-calponin in PC3-M cells effectively inhibited cell proliferation and migration. The results suggest that the diminished expression of h2-calponin in prostate cancer cells increases cell motility, decreases substrate adhesion, and promotes adhesion on high stiffness substrates.
authors.affiliation: Department of Physiology, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: M
authors.initials: M
authors.lastname: Moazzem Hossain
authors.affiliation: Department of Physiology, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Raymond C
authors.initials: RC
authors.lastname: Bergan
authors.affiliation: Department of Physiology, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: J-P
authors.initials: JP
authors.lastname: Jin
keywords: Cell motility; Cytoskeleton; FBS, fetal bovine serum; H2-calponin; MES, 2-[N morpholino]ethanesulfonic acid; Mechanical regulation; PBS, phosphate buffered saline; SDS–PAGE, SDS–polyacrylamide gel electrophoresis; Substrate stiffness; mAb, monoclonal antibody