Hepatocyte growth factor/scatter factor effects on epithelia. Regulation of intercellular junctions in transformed and nontransformed cell lines, basolateral polarization of c-met receptor in transformed and natural intestinal epithelia, and induction of rapid wound repair in a transformed model epithelium.

Depending on the target cells and culture conditions, scatter factor/hepatocyte growth factor (SF/HGF) mediates several distinct activities, i.e., cell motility, proliferation, invasiveness, tubular morphogenesis, angiogenesis, or cytotoxicity. A small isoform of SF/HGF encoded by a natural splice variant, which consists of the NH2-terminal hairpin structure and the first two kringle domains but not the protease homology region, induces cell motility but not mitogenesis. Two types of SF/HGF receptors have recently been discovered in epithelial cells, the high affinity c-Met receptor tyrosine kinase, and low affinity/high capacity binding sites, which are probably located on heparan sulfate proteoglycans. In the present study, we have addressed the question whether the various biological activities of SF/HGF are transduced into cells by a single type of receptor. We have here examined MDCK epithelial cells transfected with a hybrid cDNA encoding the ligand binding domain of the nerve growth factor (NGF) receptor and the membrane-spanning and tyrosine kinase domains of the Met receptor. We demonstrate that all biological effects of SF/HGF upon epithelial cells such as the induction of cell motility, proliferation, invasiveness, and tubular morphogenesis can now be triggered by the addition of NGF. Thus, it is likely that all known biological signals of SF/HGF are transduced through the receptor tyrosine kinase encoded by the c-Met protooncogene.

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The roles of hepatocyte growth factor/scatter factor and met receptor in human cancers (Review).

Oncology Reports ◽

10.3892/or.5.5.1013 ◽

1998 ◽

Cited By ~ 5

Author(s):

C T To ◽

M S Tsao

Keyword(s):

Growth Factor ◽

Hepatocyte Growth Factor ◽

Met Receptor ◽

Scatter Factor ◽

Human Cancers ◽

Hepatocyte Growth

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Neoexpression of the c-met/Hepatocyte Growth Factor-Scatter Factor Receptor Gene in Activated Monocytes

Blood ◽

10.1182/blood.v90.11.4450.4450_4450_4458 ◽

1997 ◽

Vol 90 (11) ◽

pp. 4450-4458 ◽

Cited By ~ 1

Author(s):

Mario Beilmann ◽

Margarete Odenthal ◽

Waltraud Jung ◽

George F. Vande Woude ◽

Hans-Peter Dienes ◽

...

Keyword(s):

Growth Factor ◽

Hepatocyte Growth Factor ◽

Cell Lines ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Cell Function ◽

Myeloid Cell ◽

Scatter Factor ◽

Activated Monocytes ◽

Hepatocyte Growth

Hepatocyte growth factor-scatter factor (HGF-SF ) mediates mito-, moto-, and morphogenic effects through the MET receptor, a membrane bound tyrosine kinase. HGF-SF/MET signaling is mitogenic for a large number of epithelial and endothelial cells and activates organ regeneration. HGF-SF transcripts have been detected in various myeloid cell lines. Therefore, the potential role of HGF-SF/MET signaling for circulating cells of the immune system, especially under conditions of inflammation, was evaluated. Several B-lymphoid and myeloid cell lines were found to express HGF-SF or c-met transcripts, while activity of both genes was mutually exclusive with the exception of low level coexpression in two B-cell lines. HGF-SF transcripts were present in low quantities in freshly isolated peripheral blood mononuclear cells (PBMNCs). In contrast, c-met expression was not detected in freshly isolated cells from peripheral blood, but was induced in monocytes by activation of monocytic or T-cell function. HGF-SF incubation led to an increased c-fos steady state transcript level in myeloblastic K562 cells and moderately promoted cell viability of freshly isolated preactivated monocytes. c-met expression is thus established in activated monocytes, in particular under conditions resembling inflammation, making these cells accessible to functional effects of HGF-SF.

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