PMID- 8522613 OWN - NLM STAT- MEDLINE DCOM- 19960123 LR - 20190508 IS - 0021-9525 (Print) IS - 1540-8140 (Electronic) IS - 0021-9525 (Linking) VI - 131 IP - 6 Pt 1 DP - 1995 Dec TI - Hepatocyte growth factor/scatter factor induces a variety of tissue-specific morphogenic programs in epithelial cells. PG - 1573-86 AB - Hepatocyte growth factor/scatter factor (HGF/SF) is the mesenchymal ligand of the epithelial tyrosine kinase receptor c-Met. In vitro, HGF/SF has morphogenic properties, e.g., induces kidney epithelial cells to form branching ducts in collagen gels. Mutation of the HGF/SF gene in mice results in embryonic lethality due to severe liver and placenta defects. Here, we have evaluated the morphogenic activity of HGF/SF with a large variety of epithelial cells grown in three-dimensional collagen matrices. We found that HGF/SF induces SW 1222 colon carcinoma cells to form crypt-like structures. In these organoids, cells exhibit apical/basolateral polarity and build a well-developed brush border towards the lumen. Capan 2 pancreas carcinoma cells, upon addition of HGF/SF, develop large hollow spheroids lined with a tight layer of polarized cells. Collagen inside the cysts is digested and the cells show features of pancreatic ducts. HGF/SF induces EpH4 mammary epithelial cells to form long branches with end-buds that resemble developing mammary ducts. pRNS-1-1 prostate epithelial cells in the presence of HGF/SF develop long ducts with distal branching as found in the prostate. Finally, HGF/SF simulates alveolar differentiation in LX-1 lung carcinoma cells. Expression of transfected HGF/SF cDNA in LX-1 lung carcinoma and EpH4 mammary epithelial cells induce morphogenesis in an autocrine manner. In the cell lines tested, HGF/SF activated the Met receptor by phosphorylation of tyrosine residues. These data show that HGF/SF induces intrinsic, tissue-specific morphogenic activities in a wide variety of epithelial cells. Apparently, HGF/SF triggers respective endogenous programs and is thus an inductive, not an instructive, mesenchymal effector for epithelial morphogenesis. FAU - Brinkmann, V AU - Brinkmann V AD - Max-Delbruck-Center for Molecular Medicine, Berlin, Germany. FAU - Foroutan, H AU - Foroutan H FAU - Sachs, M AU - Sachs M FAU - Weidner, K M AU - Weidner KM FAU - Birchmeier, W AU - Birchmeier W LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Cell Biol JT - The Journal of cell biology JID - 0375356 RN - 0 (Proto-Oncogene Proteins) RN - 67256-21-7 (Hepatocyte Growth Factor) RN - EC 2.7.10.1 (Proto-Oncogene Proteins c-met) RN - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases) SB - IM MH - Adenocarcinoma MH - Animals MH - Carcinoma MH - Cell Size/physiology MH - Colonic Neoplasms MH - Dogs MH - Embryonic and Fetal Development/physiology MH - Epithelial Cells MH - Epithelium/physiology/ultrastructure MH - Hepatocyte Growth Factor/*physiology MH - Humans MH - Kidney/cytology MH - Liver/*cytology/*growth & development MH - Lung/cytology MH - Male MH - Mice MH - Microscopy, Electron MH - Morphogenesis/physiology MH - Pancreas/cytology MH - Phosphorylation MH - Prostate/cytology MH - Proto-Oncogene Proteins/metabolism MH - Proto-Oncogene Proteins c-met MH - Receptor Protein-Tyrosine Kinases/metabolism MH - Tumor Cells, Cultured/cytology/physiology/ultrastructure PMC - PMC2120656 EDAT- 1995/12/01 00:00 MHDA- 1995/12/01 00:01 PMCR- 1996/06/02 CRDT- 1995/12/01 00:00 PHST- 1995/12/01 00:00 [pubmed] PHST- 1995/12/01 00:01 [medline] PHST- 1995/12/01 00:00 [entrez] PHST- 1996/06/02 00:00 [pmc-release] AID - 96101935 [pii] AID - 10.1083/jcb.131.6.1573 [doi] PST - ppublish SO - J Cell Biol. 1995 Dec;131(6 Pt 1):1573-86. doi: 10.1083/jcb.131.6.1573.