Source:http://linkedlifedata.com/resource/pubmed/id/12183053
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1-3
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pubmed:dateCreated |
2002-8-16
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pubmed:abstractText |
Hepatocyte growth factor/scatter factor (HGF/SF) can induce proliferation and motility and promote invasion of tumor cells. Since HGF/SF receptor, c-Met, is expressed by tumor cells, and since stimulation of CD44, a transmembrane glycoprotein known to bind hyaluronic acid (HA) in its extracellular domain, is involved in activation of c-Met, we have studied the effects of CD44 stimulation by ligation with HA upon the expression and tyrosine phosphorylation of c-Met on human chondrosarcoma cell line HCS-2/8. The current study indicates that (a) CD44 stimulation by fragmented HA upregulates expression of c-Met proteins; (b) fragmented HA also induces tyrosine phosphorylation of c-Met protein within 30 min, an early event in this pathway as shown by the early time course of stimulation; (c) the effects of HA fragments are critically HA size-dependent. High molecular weight HA is inactive, but lower molecular weight fragments (M(r) 3.5 kDa) are active with maximal effect in the microg/ml range; (d) the standard form of CD44 (CD44s) is critical for the response because the effect on c-Met, both in terms of upregulation and phosphorylation, is inhibited by preincubation with an anti-CD44 monoclonal antibody; and (e) phosphorylation of c-Met induced by CD44 stimulation is inhibited by protein tyrosine kinase inhibitor, tyrphostin. Therefore, our study represents the first report that CD44 stimulation induced by fragmented HA enhances c-Met expression and tyrosine phosphorylation in human chondrosarcoma cells. Taken together, these studies establish a signal transduction cascade or cross-talk emanating from CD44 to c-Met.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0006-3002
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
19
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pubmed:volume |
1591
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
37-44
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:12183053-Antigens, CD44,
pubmed-meshheading:12183053-Chondrosarcoma,
pubmed-meshheading:12183053-Dose-Response Relationship, Drug,
pubmed-meshheading:12183053-Humans,
pubmed-meshheading:12183053-Hyaluronic Acid,
pubmed-meshheading:12183053-Phosphorylation,
pubmed-meshheading:12183053-Proto-Oncogene Proteins c-met,
pubmed-meshheading:12183053-Tumor Cells, Cultured,
pubmed-meshheading:12183053-Tyrosine,
pubmed-meshheading:12183053-Up-Regulation
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pubmed:year |
2002
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pubmed:articleTitle |
CD44 stimulation by fragmented hyaluronic acid induces upregulation and tyrosine phosphorylation of c-Met receptor protein in human chondrosarcoma cells.
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pubmed:affiliation |
Department of Obstetrics and Gynecology, Hamamatsu University School of Medicine, Handayama 1-20-1, Handacho 3600, Hamamatsu, Shizuoka 431-3192, Japan.
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pubmed:publicationType |
Journal Article
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