PMID- 11485916 OWN - NLM STAT- MEDLINE DCOM- 20010906 LR - 20220317 IS - 0002-9440 (Print) IS - 1525-2191 (Electronic) IS - 0002-9440 (Linking) VI - 159 IP - 2 DP - 2001 Aug TI - Normal and malignant prostate epithelial cells differ in their response to hepatocyte growth factor/scatter factor. PG - 579-90 AB - Hepatocyte growth factor/scatter factor (HGF/SF) promotes the proliferation, differentiation, motility, and invasion of epithelial cells by binding to its cell surface receptor, the Met tyrosine kinase. In the prostate, Met is expressed predominantly by prostate epithelial cells (PrEC), whereas HGF/SF is synthesized by prostate stromal cells (PrSC). Met is also expressed in localized and metastatic prostate cancers. Our results show that PrECs in in vitro culture maintain expression of Met at a level comparable to DU145 cancer cell expression. HGF/SF secreted by PrSC stimulates tyrosine phosphorylation of the Met receptor. In normal PrEC, HGF/SF causes growth inhibition, sustained phosphorylation of mitogen-activated protein kinase, and increased CK18 expression consistent with cell differentiation. In contrast, HGF/SF significantly stimulates the proliferation of DU145 prostate cancer cells. HGF/SF in the conditioned medium of PrSC specifically induces migration of both normal and malignant prostate epithelial cells through MatriGel-coated Transwell filters. HGF/SF depletion reduces cell migration by approximately 50%. The response of PrEC is specific for HGF/SF since the other growth factors tested do not significantly affect growth or migration of PrECs. These results support the in vivo importance of the prostate stroma and specifically of HGF/SF as a unique stromal derived factor in the development and progression of prostate cancer. FAU - Gmyrek, G A AU - Gmyrek GA AD - Department of Pathology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA. FAU - Walburg, M AU - Walburg M FAU - Webb, C P AU - Webb CP FAU - Yu, H M AU - Yu HM FAU - You, X AU - You X FAU - Vaughan, E D AU - Vaughan ED FAU - Vande Woude, G F AU - Vande Woude GF FAU - Knudsen, B S AU - Knudsen BS LA - eng PT - Journal Article PT - Research Support, U.S. Gov't, Non-P.H.S. PL - United States TA - Am J Pathol JT - The American journal of pathology JID - 0370502 RN - 0 (Culture Media, Conditioned) RN - 0 (Desmin) RN - 0 (Drug Combinations) RN - 0 (Laminin) RN - 0 (Proteoglycans) RN - 0 (Receptors, Androgen) RN - 0 (Vimentin) RN - 119978-18-6 (matrigel) RN - 67256-21-7 (Hepatocyte Growth Factor) RN - 68238-35-7 (Keratins) RN - 9007-34-5 (Collagen) SB - IM MH - Animals MH - Cell Differentiation MH - Cell Division/drug effects MH - Cell Line MH - Cell Movement/drug effects/physiology MH - Cells, Cultured MH - Collagen MH - Culture Media, Conditioned MH - Desmin/analysis/genetics MH - Dogs MH - Drug Combinations MH - Epithelial Cells/cytology/*drug effects/pathology MH - Hepatocyte Growth Factor/analysis/*genetics/*pharmacology MH - Humans MH - Immunohistochemistry MH - Keratins/analysis/genetics MH - Laminin MH - Male MH - Prostate/*cytology/drug effects/pathology MH - Prostatic Neoplasms/*pathology MH - Proteoglycans MH - Receptors, Androgen/analysis/genetics MH - Reverse Transcriptase Polymerase Chain Reaction MH - Tumor Cells, Cultured MH - Vimentin/analysis/genetics PMC - PMC1850543 EDAT- 2001/08/04 10:00 MHDA- 2001/09/08 10:01 PMCR- 2002/02/01 CRDT- 2001/08/04 10:00 PHST- 2001/08/04 10:00 [pubmed] PHST- 2001/09/08 10:01 [medline] PHST- 2001/08/04 10:00 [entrez] PHST- 2002/02/01 00:00 [pmc-release] AID - S0002-9440(10)61729-4 [pii] AID - 2779 [pii] AID - 10.1016/S0002-9440(10)61729-4 [doi] PST - ppublish SO - Am J Pathol. 2001 Aug;159(2):579-90. doi: 10.1016/S0002-9440(10)61729-4.