RRC ID |
39370
|
著者 |
Hamasuna R, Kataoka H, Moriyama T, Itoh H, Seiki M, Koono M.
|
タイトル |
Regulation of matrix metalloproteinase-2 (MMP-2) by hepatocyte growth factor/scatter factor (HGF/SF) in human glioma cells: HGF/SF enhances MMP-2 expression and activation accompanying up-regulation of membrane type-1 MMP.
|
ジャーナル |
Int J Cancer
|
Abstract |
Hepatocyte growth factor/scatter factor (HGF/SF) contributes to the malignant progression of human gliomas. We investigated the effect of HGF/SF on matrix metalloproteinase-2 (MMP-2), membrane type 1 matrix metalloproteinase (MT1-MMP) and tissue inhibitors of metalloproteinases (TIMPs), expressions of c-Met/HGF receptor-positive human glioblastoma cells. Treatment of U251 human glioblastoma cells with HGF/SF resulted in enhanced secretion of MMP-2 with an increased level of the active form. This was accompanied by enhanced expression (2.5-fold) of mRNA specific for MMP-2. The stimulatory effect of HGF/SF on MMP-2 expression did not occur in the presence of herbimycin A, a protein tyrosine kinase inhibitor. MT1 -MMP, a cell-surface activator of proMMP-2, was also up-regulated by HGF/SF in a dose-dependent manner. By contrast, the level of TIMP- 1 mRNAs was not altered significantly and that of TIMP-2 was reduced mildly by the HGF/SF treatment, suggesting that HGF/SF may eventually modulate a balance between MMP-2 and TIMPs in favor of the proteinase activity in the glioma cell microenvironment. HGF/SF also stimulated MMP-2 expression of other glioblastoma cell lines. Since glioblastomas frequently co-express HGF/SF and its receptor, our results suggest that HGF/SF might contribute to the invasiveness of glioblastoma cells through autocrine induction of MMP-2 expression and activation.
|
巻・号 |
82(2)
|
ページ |
274-81
|
公開日 |
1999-7-19
|
DOI |
10.1002/(sici)1097-0215(19990719)82:2<274::aid-ijc19>3.0.co;2-2
|
PII |
10.1002/(SICI)1097-0215(19990719)82:2<274::AID-IJC19>3.0.CO;2-2
|
PMID |
10389763
|
MeSH |
Benzoquinones
Brain Neoplasms / enzymology
Brain Neoplasms / genetics
Brain Neoplasms / pathology*
Disease Progression
Enzyme Induction / drug effects
Enzyme Inhibitors / pharmacology
Epidermal Growth Factor / pharmacology
Gelatinases / biosynthesis*
Gelatinases / genetics
Gene Expression Regulation, Neoplastic / drug effects*
Glioblastoma / enzymology
Glioblastoma / genetics
Glioblastoma / pathology
Glioma / enzymology
Glioma / genetics
Glioma / pathology*
Hepatocyte Growth Factor / pharmacology*
Humans
Lactams, Macrocyclic
Matrix Metalloproteinase 2
Matrix Metalloproteinases, Membrane-Associated
Metalloendopeptidases / biosynthesis*
Metalloendopeptidases / genetics
Neoplasm Invasiveness
Neoplasm Proteins / biosynthesis*
Neoplasm Proteins / genetics
Protein-Tyrosine Kinases / antagonists & inhibitors
Quinones / pharmacology
RNA, Messenger / biosynthesis
RNA, Messenger / genetics
RNA, Neoplasm / biosynthesis
RNA, Neoplasm / genetics
Recombinant Proteins / pharmacology
Rifabutin / analogs & derivatives
Signal Transduction / drug effects
Stimulation, Chemical
Tumor Cells, Cultured
|
IF |
5.145
|
引用数 |
58
|
WOS 分野
|
ONCOLOGY
|
リソース情報 |
ヒト・動物細胞 |
U251(RCB0461) |