PMID- 12915116 OWN - NLM STAT- MEDLINE DCOM- 20031017 LR - 20211203 IS - 0014-4827 (Print) IS - 0014-4827 (Linking) VI - 288 IP - 2 DP - 2003 Aug 15 TI - Regulation of migration of primary prostate epithelial cells by secreted factors from prostate stromal cells. PG - 246-56 AB - 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. FAU - You, Xueke AU - You X AD - Department of Pathology, Weill Medical College of Cornell University, New York, NY 10021, USA. FAU - Yu, Hsiao-Man AU - Yu HM FAU - Cohen-Gould, Leona AU - Cohen-Gould L FAU - Cao, Brian AU - Cao B FAU - Symons, Marc AU - Symons M FAU - Vande Woude, George F AU - Vande Woude GF FAU - Knudsen, Beatrice S AU - Knudsen BS LA - eng PT - Journal Article PT - Research Support, U.S. Gov't, Non-P.H.S. PL - United States TA - Exp Cell Res JT - Experimental cell research JID - 0373226 RN - 0 (Culture Media, Conditioned) RN - 0 (Enzyme Inhibitors) RN - 0 (Extracellular Matrix Proteins) RN - 0 (Proto-Oncogene Proteins) RN - 67256-21-7 (Hepatocyte Growth Factor) RN - EC 2.7.11.1 (AKT1 protein, human) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM MH - Animals MH - Cell Adhesion/physiology MH - Cell Movement/*physiology MH - Cell Polarity MH - Cells, Cultured MH - Culture Media, Conditioned MH - Enzyme Inhibitors/metabolism MH - Epithelial Cells/*physiology MH - Extracellular Matrix Proteins/metabolism MH - Hepatocyte Growth Factor/metabolism MH - Humans MH - Male MH - Phosphatidylinositol 3-Kinases/metabolism MH - Prostate/*cytology/metabolism MH - *Protein Serine-Threonine Kinases MH - Proto-Oncogene Proteins/metabolism MH - Proto-Oncogene Proteins c-akt MH - Signal Transduction/physiology MH - Stromal Cells/*metabolism EDAT- 2003/08/14 05:00 MHDA- 2003/10/18 05:00 CRDT- 2003/08/14 05:00 PHST- 2003/08/14 05:00 [pubmed] PHST- 2003/10/18 05:00 [medline] PHST- 2003/08/14 05:00 [entrez] AID - S0014482703002040 [pii] AID - 10.1016/s0014-4827(03)00204-0 [doi] PST - ppublish SO - Exp Cell Res. 2003 Aug 15;288(2):246-56. doi: 10.1016/s0014-4827(03)00204-0.