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Hepatocyte growth factor/scatter factor induces a variety of tissue-specific morphogenic programs in epithelial cells

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Item Type:Article
Title:Hepatocyte growth factor/scatter factor induces a variety of tissue-specific morphogenic programs in epithelial cells
Creators Name:Brinkmann, V. and Foroutan, H. and Sachs, M. and Weidner, K.M. and Birchmeier, W.
Abstract: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.
Keywords:Adenocarcinoma, Carcinoma, Cell Size, Colonic Neoplasms, Cultured Tumor Cells, Electron Microscopy, Embryonic and Fetal Development, Epithelial Cells, Epithelium, Hepatocyte Growth Factor, Kidney, Liver, Lung, Morphogenesis, Pancreas, Phosphorylation, Prostate, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-Met, Receptor Protein-Tyrosine Kinases, Animals, Dogs, Mice
Source:Journal of Cell Biology
ISSN:0021-9525
Publisher:Rockefeller University Press (U.S.A.)
Volume:131
Number:6 Pt. 1
Page Range:1573-1586
Date:December 1995
Additional Information:Copyright (c) 1995 by The Rockefeller University Press
Official Publication:http://www.jcb.org/cgi/reprint/131/6/1573
PubMed:View item in PubMed

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