PMID- 9524767
OWN - NLM
STAT- MEDLINE
DCOM- 19980518
LR  - 20190905
IS  - 0300-5208 (Print)
IS  - 0300-5208 (Linking)
VI  - 212
DP  - 1997
TI  - Met-HGF/SF: tumorigenesis, invasion and metastasis.
PG  - 119-30; discussion 130-2, 148-54
AB  - Hepatocyte growth factor/scatter factor (HGF/SF) is synthesized by mesenchymal 
      cells and is a paracrine effector of cells, predominantly epithelial, that 
      express the Met tyrosine kinase receptor. We have demonstrated that autocrine 
      Met-HGF/SF expression in mouse fibroblasts results in transformation and 
      tumorigenesis. HGF/SF-treated cells expressing Met can respond in a variety of 
      ways: mitogenically, by scattering (motility), and by forming branching tubules 
      in gel matrices (branching morphogenesis). HGF/SF also induces in vitro 
      invasiveness and is angiogenic in in vivo assays. A human cell line and several 
      mouse cell lines that we have constructed to express Met-HGF/SF in an autocrine 
      fashion are tumorigenic, invasive and metastatic in athymic nude mice. Thus, the 
      very complex process of invasion and metastasis can be mediated by a 
      ligand-receptor signalling pathway, and the cell lines we have developed provide 
      important model systems for identifying the signalling molecules that mediate 
      these phenotypes: For example Met-HGF/SF signalling activates the urokinase 
      plasminogen proteolysis network, thus coupling this signal transduction pathway 
      to the proteases that mediate dissolution of the extracellular matrix. Branching 
      morphogenesis, mediated by Met-HGF/SF signalling, is dependent on this process, 
      as well as the formation of cell-cell junctions and interaction with the 
      extracellular matrix. We have proposed a hypothesis for the role of Met and 
      downstream signalling molecules in generating normal ducts and lumenal 
      structures, as well as a model for how interruption of this signalling leads to 
      abnormal malignant progression. Is Met involved in human cancer? Human sarcomas 
      often inappropriately express Met, suggesting that it is an important oncogene in 
      these cancers, and an increasing number of reports have implicated Met-HGF/SF 
      signalling in a variety of human cancers.
FAU - Vande Woude, G F
AU  - Vande Woude GF
AD  - ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, 
      MD 21702, USA.
FAU - Jeffers, M
AU  - Jeffers M
FAU - Cortner, J
AU  - Cortner J
FAU - Alvord, G
AU  - Alvord G
FAU - Tsarfaty, I
AU  - Tsarfaty I
FAU - Resau, J
AU  - Resau J
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Review
PL  - Netherlands
TA  - Ciba Found Symp
JT  - Ciba Foundation symposium
JID - 0356636
RN  - 0 (Receptors, Cell Surface)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - EC 2.7.10.1 (RON protein)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
SB  - IM
MH  - Animals
MH  - Autocrine Communication
MH  - Cell Line, Transformed
MH  - Hepatocyte Growth Factor/*biosynthesis
MH  - Humans
MH  - Neoplasm Invasiveness
MH  - Neoplasm Metastasis
MH  - Neoplasms/*metabolism/pathology
MH  - Receptor Protein-Tyrosine Kinases/*biosynthesis
MH  - Receptors, Cell Surface/*biosynthesis
MH  - Signal Transduction/physiology
RF  - 40
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.ch8 [doi]
PST - ppublish
SO  - Ciba Found Symp. 1997;212:119-30; discussion 130-2, 148-54. doi: 
      10.1002/9780470515457.ch8.