Association of extracellular cleavage of E-cadherin mediated by MMP-7 with HGF-induced in vitro invasion in human stomach cancer cells.
BACKGROUND
Proteolytic shedding of the ectodomain of a variety of transmembrane proteins, including cell-to-cell adhesion molecules, has been observed in solid cancers. We have investigated whether extracellular cleavage of E-cadherin mediated by matrix metalloproteinase-7 (MMP-7) is involved in hepatocyte growth factor (HGF) induced in vitro invasion in stomach cancer cells.


METHODS
The effects of HGF on the expression of E-cadherin/beta-catenin and MMP-7 at both the protein and mRNA levels were assessed in stomach cancer cells, NUGC-3 and MKN-28, and in cells in which the expression of MMP-7 was downregulated by transfection with a MMP-7 short hairpin RNA plasmid.


RESULTS
Treatment with HGF increased the extracellular cleavage of E-cadherin and the release of MMP-7 and reduced the level of E-cadherin in a dose- and time-dependent manner. HGF treatment repressed the phosphorylation of beta-catenin in a Triton-soluble fraction, but enhanced this phosphorylation in a Triton-insoluble fraction. The association of E-cadherin with beta-catenin was decreased by HGF treatment in the Triton-soluble fraction. In addition, treatment of MMP-7 short hairpin RNA transfected NUGC-3 cells with HGF resulted in no extracellular cleavage of E-cadherin and also decreased the in vitro cell invasion.


CONCLUSIONS
These results suggest that incubation with HGF mediated the release of MMP-7, resulting in extracellular cleavage of E-cadherin from stomach cancer cells. This might be a key mechanism in HGF-induced in vitro invasion and metastasis.
Lee
K H
KH
Department of Hemato-Oncology, College of Medicine, Yeungnam University, Daegu, Republic of Korea.
Choi
E Y
EY
Hyun
M S
MS
Jang
B I
BI
Kim
T N
TN
Kim
S W
SW
Song
S K
SK
Kim
J H
JH
Kim
J-R
JR
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D015820:Cadherins / Q000378:metabolism*; D045744:Cell Line, Tumor; D003902:Detergents; D004789:Enzyme Activation / Q000187:drug effects; D005110:Extracellular Space / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D020783:Matrix Metalloproteinase 7 / Q000235:genetics / Q000378:metabolism*; D016296:Mutagenesis; D009361:Neoplasm Invasiveness / Q000473:pathology; D017830:Octoxynol; D010766:Phosphorylation / Q000187:drug effects; D012995:Solubility; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D051176:beta Catenin / Q000378:metabolism
D015820:Cadherins; D003902:Detergents; D051176:beta Catenin; D017228:Hepatocyte Growth Factor; D017830:Octoxynol; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7