scholarly journals Expression of a human hepatocyte growth factor/scatter factor cDNA in MDCK epithelial cells influences cell morphology, motility, and anchorage-independent growth

1992 ◽  
Vol 117 (4) ◽  
pp. 889-894 ◽  
Author(s):  
Y Uehara ◽  
N Kitamura
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Hepatocyte Growth Factor ◽  
Cell Motility ◽  
Mdck Cells ◽  
Soft Agar ◽  
Scatter Factor ◽  
Anchorage Independent Growth ◽  
Surface Receptors ◽  
Hepatocyte Growth

The addition of exogenous hepatocyte growth factor (HGF)/scatter factor (SF) to MDCK epithelial cells results in fibroblastic morphology and cell motility. We generated HGF/SF producing MDCK cells by transfection with an expression plasmid containing human HGF/SF cDNA. Production of HGF/SF by these cells induced a change from an epithelial to a fibroblastic morphology and increased cell motility. In addition, the HGF/SF producing cells acquired efficient anchorage-independent growth in soft agar but did not form tumors in nude mice. The morphological change and the stimulation of the anchorage-independent growth were prevented by anti-HGF/SF antibody, suggesting that the factor is secreted and then exerts its effects through cell surface receptors.

scholarly journals The Met receptor tyrosine kinase transduces motility, proliferation, and morphogenic signals of scatter factor/hepatocyte growth factor in epithelial cells.

1993 ◽  
Vol 121 (1) ◽  
pp. 145-154 ◽  
Author(s):  
K M Weidner ◽  
M Sachs ◽  
W Birchmeier
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Hepatocyte Growth Factor ◽  
Tyrosine Kinase ◽  
Cell Motility ◽  
Receptor Tyrosine Kinase ◽  
Met Receptor ◽  
Scatter Factor ◽  
Met Receptor Tyrosine Kinase ◽  
Hepatocyte Growth

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.

scholarly journals Normal and Malignant Prostate Epithelial Cells Differ in Their Response to Hepatocyte Growth Factor/Scatter Factor

2001 ◽  
Vol 159 (2) ◽  
pp. 579-590 ◽  
Author(s):  
Glenn A. Gmyrek ◽  
Marc Walburg ◽  
Craig P. Webb ◽  
Hsiao-Man Yu ◽  
Xueke You ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Hepatocyte Growth Factor ◽  
Scatter Factor ◽  
Prostate Epithelial Cells ◽  
Hepatocyte Growth ◽  
Malignant Prostate

scholarly journals Scatter factor/hepatocyte growth factor and its receptor, the c-met tyrosine kinase, can mediate a signal exchange between mesenchyme and epithelia during mouse development.

1993 ◽  
Vol 123 (1) ◽  
pp. 223-235 ◽  
Author(s):  
E Sonnenberg ◽  
D Meyer ◽  
K M Weidner ◽  
C Birchmeier
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Hepatocyte Growth Factor ◽  
Tyrosine Kinase ◽  
Cell Surface Receptor ◽  
Mouse Development ◽  
Scatter Factor ◽  
Rnase Protection ◽  
Hepatocyte Growth

Scatter factor/hepatocyte growth factor (SF/HGF) has potent motogenic, mitogenic, and morphogenetic activities on epithelial cells in vitro. The cell surface receptor for this factor was recently identified: it is the product of the c-met protooncogene, a receptor-type tyrosine kinase. We report here the novel and distinct expression patterns of SF/HGF and its receptor during mouse development, which was determined by a combination of in situ hybridization and RNase protection experiments. Predominantly, we detect transcripts of c-met in epithelial cells of various developing organs, whereas the ligand is expressed in distinct mesenchymal cells in close vicinity. In addition, transient SF/HGF and c-met expression is found at certain sites of muscle formation; transient expression of the c-met gene is also detected in developing motoneurons. SF/HGF and the c-met receptor might thus play multiple developmental roles, most notably, mediate a signal given by mesenchyme and received by epithelial. Mesenchymal signals are known to govern differentiation and morphogenesis of many epithelia, but the molecular nature of the signals has remained poorly understood. Therefore, the known biological activities of SF/HGF in vitro and the embryonal expression pattern reported here indicate that this mesenchymal factor can transmit morphogenetic signals in epithelial development and suggest a molecular mechanism for mesenchymal epithelial interactions.

scholarly journals Sequential Activation of ERK and Repression of JNK by Scatter Factor/Hepatocyte Growth Factor in Madin-Darby Canine Kidney Epithelial Cells

2000 ◽  
Vol 11 (11) ◽  
pp. 3751-3763 ◽  
Author(s):  
Réjane Paumelle ◽  
David Tulasne ◽  
Catherine Leroy ◽  
Jean Coll ◽  
Bernard Vandenbunder ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Hepatocyte Growth Factor ◽  
Cell Density ◽  
Transcriptional Response ◽  
Madin Darby Canine Kidney ◽  
Scatter Factor ◽  
Hepatocyte Growth ◽  
Darby Canine Kidney ◽  
Canine Kidney

The scattering of Madin-Darby canine kidney (MDCK) epithelial cells by scatter factor/hepatocyte growth factor (SF/HGF) is associated with transcriptional induction of the urokinase gene, which occurs essentially through activation of an EBS/AP1 response element. We have investigated the signal transduction pathways leading to this transcriptional response. We found that SF/HGF induces rapid and sustained phosphorylation of the extracellular signal-regulated kinase (ERK) MAPK while stimulating weakly and then repressing phosphorylation of the JUN N-terminal kinase (JNK) MAPK for several hours. This delayed repression of JNK was preceded by phosphorylation of the MKP2 phosphatase, and both MKP2 induction and JNK dephosphorylation were under the control of MEK, the upstream kinase of ERK. ERK and MKP2 stimulate the EBS/AP1-dependent transcriptional response to SF/HGF, but not JNK, which inhibits this response. We further demonstrated that depending on cell density, the RAS-ERK-MKP2 pathway controls this transrepressing effect of JNK. Together, these data demonstrate that in a sequential manner SF/HGF activates ERK and MKP2, which in turn dephosphorylates JNK. This sequence of events provides a model for efficient cell scattering by SF/HGF at low cell density.

Effect of scatter factor and hepatocyte growth factor on motility and morphology of mdck cells

1992 ◽  
Vol 28 (5) ◽  
pp. 364-368 ◽  
Author(s):  
Yuan LI ◽  
Ansamma Joseph ◽  
Madhu M. Bhargava ◽  
Eliot M. Rosen ◽  
Toshikazu Nakamura ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Mdck Cells ◽  
Scatter Factor ◽  
Hepatocyte Growth

Comparison of biological and immunochemical properties indicates that scatter factor and hepatocyte growth factor are indistinguishable

1991 ◽  
Vol 100 (1) ◽  
pp. 173-177 ◽  
Author(s):  
R.A. Furlong ◽  
T. Takehara ◽  
W.G. Taylor ◽  
T. Nakamura ◽  
J.S. Rubin
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Cell Motility ◽  
Recombinant Proteins ◽  
Sequence Data ◽  
Biological Activities ◽  
Scatter Factor ◽  
Naturally Occurring ◽  
Biological Studies ◽  
Hepatocyte Growth

Scatter factor, a stimulant of epithelial cell motility, and Hepatocyte Growth Factor (HGF) were compared by cross-biological studies using naturally occurring and recombinant proteins in four bioassays. Both scatter factor and HGF produced similar effects in cell motility and DNA synthesis assays. Antibodies to scatter factor or HGF neutralized the biological activities of each cytokine, and in immunoblotting reacted with species of the same Mr. These results, together with the available sequence data, suggest that scatter factor and HGF are the same protein.

Loss of MDCK cell alpha 2 beta 1 integrin expression results in reduced cyst formation, failure of hepatocyte growth factor/scatter factor-induced branching morphogenesis, and increased apoptosis

1995 ◽  
Vol 108 (11) ◽  
pp. 3531-3540 ◽  
Author(s):  
E.U. Saelman ◽  
P.J. Keely ◽  
S.A. Santoro
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Antisense Rna ◽  
Mdck Cells ◽  
Cyst Formation ◽  
Branching Morphogenesis ◽  
Integrin Subunit ◽  
Scatter Factor ◽  
Beta 1 Integrin ◽  
Hepatocyte Growth

Cellular interactions with collagen in a model of kidney tubulogenesis were investigated using Madin-Darby canine kidney (MDCK) cells in an in vitro morphogenetic system. MDCK cells adhered to collagen types I and IV in a Mg(2+)-dependent manner, typical of the alpha 2 beta 1 integrin. Collagen-Sepharose affinity chromatography and immunoblotting demonstrated the presence and collagen binding activity of the alpha 2 beta 1 integrin on MDCK cells. To assess the function of alpha 2 beta 1 integrin, MDCK cells were transfected with a plasmid pRSV alpha 2′ which allowed the expression of alpha 2-integrin subunit antisense RNA. Three G418-resistant clones showing reduced adhesion to collagen, stable genomic integration of the antisense construct, decreased alpha 2-integrin subunit mRNA and decreased alpha 2-integrin subunit protein expression were selected for analysis in morphogenetic experiments. MDCK cells and plasmid-only control transfectants, cultured in three-dimensional collagen type I gels, showed normal cyst formation, whereas the antisense RNA transfectants showed increased apoptosis and formed small rudimentary cysts. Stimulation with hepatocyte growth factor/scatter factor-containing 3T3 fibroblast-conditioned medium or recombinant hepatocyte growth factor/scatter factor resulted in extensive branching of the preformed control cysts whereas the surviving small cysts formed by antisense expressing cells increased in size but failed to elongate and branch upon stimulation. We conclude that alpha 2 beta 1 integrin collagen interactions play a crucial role in the hepatocyte growth factor/scatter factor-induced tubulogenesis and branching morphogenesis of MDCK cells in collagen gels as well as an important role in cell survival.

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