title: Regulation of migration of primary prostate epithelial cells by secreted factors from prostate stromal cells.
abstract: Stromal-epithelial interactions, which regulate the migration of prostate epithelial cells, play an important role in prostate development, prostatic hyperplasia, and prostate cancer. The objective of this study was to determine how the prostate stroma stimulates the migration of primary prostate epithelial cells (PECs). In the Boyden chamber assay, PEC migration was strongly induced by the conditioned medium of primary prostate stromal cells (PSC-CM). Stimulation of PEC migration depended on the concerted action of adhesion and motility factors in the PSC-CM. Immobilized proteins from PSC-CM mediated adhesion, spreading, and head-to-tail polarization of PECs. Migration induced by immobilized PSC-CM proteins was significantly increased by hepatocyte growth factor/scatter factor (HGF/SF). Inhibition of P13-kinase or Src-family kinases, but not MEK or PLCchi, abolished migration in the Boyden chamber assay. Consistent with their concerted activity in migration assays, the combination of adhesion and motility factors was required for efficient activation of the P13-kinase/Akt pathway. HGF/SF in the PSC-CM was the principal stimulator of the P13-kinase/Akt pathway and an important mediator of PSC-CM-induced PEC migration. In conclusion, our data show that the migration of primary PECs is regulated by the P13-kinase and Src-family kinase signaling pathways and that the activation of the P13-kinase pathway requires adhesion and motility factors from the prostate stroma.
authors.affiliation: Department of Pathology, Weill Medical College of Cornell University, New York, NY 10021, USA.
authors.forename: Xueke
authors.initials: X
authors.lastname: You
authors.forename: Hsiao-Man
authors.initials: HM
authors.lastname: Yu
authors.forename: Leona
authors.initials: L
authors.lastname: Cohen-Gould
authors.forename: Brian
authors.initials: B
authors.lastname: Cao
authors.forename: Marc
authors.initials: M
authors.lastname: Symons
authors.forename: George F
authors.initials: GF
authors.lastname: Vande Woude
authors.forename: Beatrice S
authors.initials: BS
authors.lastname: Knudsen
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D016764:Cell Polarity; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D004791:Enzyme Inhibitors / Q000378:metabolism; D004847:Epithelial Cells / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011467:Prostate / Q000166:cytology* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction / Q000502:physiology; D017154:Stromal Cells / Q000378:metabolism*
chemical_list: D017077:Culture Media, Conditioned; D004791:Enzyme Inhibitors; D016326:Extracellular Matrix Proteins; D017228:Hepatocyte Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; C494918:AKT1 protein, human