PMID- 9524774
OWN - NLM
STAT- MEDLINE
DCOM- 19980518
LR  - 20190905
IS  - 0300-5208 (Print)
IS  - 0300-5208 (Linking)
VI  - 212
DP  - 1997
TI  - Role of HGF/SF and c-Met in morphogenesis and metastasis of epithelial cells.
PG  - 230-40; discussion 240-6
AB  - We have analysed the role of hepatocyte growth factor/scatter factor (HGF/SF) in 
      the process of morphogenesis and metastasis of epithelial (carcinoma) cells. 
      HGF/SF induces various morphogenic responses in epithelial cells that derive from 
      different tissues when these are grown in three-dimensional gels, e.g. branching 
      tubules in kidney, breast, and prostate epithelial cells, crypt-like structures 
      with brush border in colon epithelial cells, and alveolar-like aggregates in lung 
      and pancreas cells. Epithelial cells are thus able to form complex structures in 
      vitro which resemble the structures formed in the organ they originate from. We 
      also examined the response of human breast carcinoma cells to HGF/SF in vivo. MDA 
      MB 435 cells transfected with HGF/SF were injected into the mammary fat pad of 
      nude mice, where they form tumours which spontaneously metastasize to the lungs. 
      We found that expression of HGF/SF promoted metastasis whereas expression of the 
      cell adhesion molecule E-cadherin was inhibitory. Moreover, expression of 
      E-cadherin reconstituted the ability of the cells to form complex structures in 
      response to HGF/SF in vitro. These data demonstrate that the different responses 
      to HGF/SF depend on the state of the epithelial cells: morphogenesis requires 
      epithelial differentiation and cell polarity, whereas metastasis is observed when 
      the cells have lost their epithelial characteristics. Moreover, we have recently 
      identified Gab-1 as a direct-binding substrate of the c-Met receptor. Gab-1 binds 
      to c-Met phosphorylated on tyrosine residues, but not to a number of other 
      tyrosine kinases from different subfamilies. A newly identified proline-rich 
      domain of Gab-1 is responsible for the binding to the bidentate docking site in 
      c-Met. Expression of Gab-1 in epithelial cells is sufficient to induce 
      c-Met-specific cellular responses which include the formation of branching 
      tubules. Thus, Gab-1 seem to correspond to the substrate of the c-Met receptor 
      tyrosine kinase that mediates the epithelial morphogenesis.
FAU - Birchmeier, W
AU  - Birchmeier W
AD  - Max-Delbruck-Center for Molecular Medicine, Berlin, Germany.
FAU - Brinkmann, V
AU  - Brinkmann V
FAU - Niemann, C
AU  - Niemann C
FAU - Meiners, S
AU  - Meiners S
FAU - DiCesare, S
AU  - DiCesare S
FAU - Naundorf, H
AU  - Naundorf H
FAU - Sachs, M
AU  - Sachs M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - Netherlands
TA  - Ciba Found Symp
JT  - Ciba Foundation symposium
JID - 0356636
RN  - 0 (Neoplasm Proteins)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
SB  - IM
MH  - Animals
MH  - Breast Neoplasms/pathology/physiopathology
MH  - Epithelial Cells/physiology
MH  - Hepatocyte Growth Factor/*physiology
MH  - Humans
MH  - Morphogenesis
MH  - Neoplasm Metastasis
MH  - Neoplasm Proteins/physiology
MH  - Proto-Oncogene Proteins c-met/*physiology
MH  - Tumor Cells, Cultured
RF  - 91
EDAT- 1997/01/01 00:00
MHDA- 1998/04/03 00:01
CRDT- 1997/01/01 00:00
PHST- 1997/01/01 00:00 [pubmed]
PHST- 1998/04/03 00:01 [medline]
PHST- 1997/01/01 00:00 [entrez]
AID - 10.1002/9780470515457.ch15 [doi]
PST - ppublish
SO  - Ciba Found Symp. 1997;212:230-40; discussion 240-6. doi: 
      10.1002/9780470515457.ch15.