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rdf:type |
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lifeskim:mentions |
umls-concept:C0003316,
umls-concept:C0007634,
umls-concept:C0008479,
umls-concept:C0017262,
umls-concept:C0033607,
umls-concept:C0042071,
umls-concept:C0070750,
umls-concept:C0086418,
umls-concept:C0185117,
umls-concept:C0205419,
umls-concept:C0332256,
umls-concept:C0597298,
umls-concept:C1332712,
umls-concept:C2911684
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pubmed:issue |
10
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pubmed:dateCreated |
2002-3-4
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pubmed:abstractText |
We previously found that bikunin (bik), a Kunitz-type protease inhibitor, suppresses phorbol ester (PMA)-stimulated expression of urokinase-type plasminogen activator (uPA). In the present study, we tried to answer this mechanism using human chondrosarcoma HCS-2/8 cells. Our results showed the following novel findings: (a) the standard form of CD44 (CD44s; 85 kDa) is expressed in both unstimulated and PMA-stimulated cells, while CD44v isoforms containing epitope v9 (110 kDa) are strongly up-regulated in response to treatment with PMA; (b) CD44v isoforms containing epitope v9 present on the same cell exclusively form aggregates in stimulated cells; (c) induction of uPA mRNA expression could be achieved by using a second cross-linker antibody to cross-link Fab monomers of anti-CD44; (d) co-treatment of stimulated cells with anti-CD44 mAb alone or anti-CD44v9 mAb alone suppresses PMA-induced clustering of CD44, which results in inhibition of uPA overexpression; (e) bikunin efficiently disrupts PMA-induced clustering of CD44, but does not prevent PMA-induced up-regulation of CD44v isoforms containing epitope v9; and (f) after exposure to bik, approximately 150-kDa band is mainly detected with immunoprecipitation and this band is shown to be a heterodimer composed of the 110-kDa v9-containing CD44v isoforms and a 45-kDa bik receptor (bik-R). In conclusion, we provide, for the first time, evidence that the bik-R can physically interact with the CD44v isoforms containing epitope v9 and function as a repressor to down-regulate PMA-stimulated uPA expression, at least in part, by preventing clustering of CD44v isoforms containing epitope v9.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD44,
http://linkedlifedata.com/resource/pubmed/chemical/Cross-Linking Reagents,
http://linkedlifedata.com/resource/pubmed/chemical/Epitopes,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Phorbol Esters,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Isoforms,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/SPINT2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Succinimides,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate,
http://linkedlifedata.com/resource/pubmed/chemical/Trypsin Inhibitor, Kunitz Soybean,
http://linkedlifedata.com/resource/pubmed/chemical/Urokinase-Type Plasminogen Activator,
http://linkedlifedata.com/resource/pubmed/chemical/disuccinimidyl suberate
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
8
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pubmed:volume |
277
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
8022-32
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:11777908-Antibodies, Monoclonal,
pubmed-meshheading:11777908-Antigens, CD44,
pubmed-meshheading:11777908-Biotinylation,
pubmed-meshheading:11777908-Blotting, Northern,
pubmed-meshheading:11777908-Blotting, Western,
pubmed-meshheading:11777908-Cell Membrane,
pubmed-meshheading:11777908-Cross-Linking Reagents,
pubmed-meshheading:11777908-Dimerization,
pubmed-meshheading:11777908-Dose-Response Relationship, Drug,
pubmed-meshheading:11777908-Down-Regulation,
pubmed-meshheading:11777908-Enzyme-Linked Immunosorbent Assay,
pubmed-meshheading:11777908-Epitopes,
pubmed-meshheading:11777908-Flow Cytometry,
pubmed-meshheading:11777908-Humans,
pubmed-meshheading:11777908-Membrane Glycoproteins,
pubmed-meshheading:11777908-Microscopy, Fluorescence,
pubmed-meshheading:11777908-Models, Biological,
pubmed-meshheading:11777908-Phorbol Esters,
pubmed-meshheading:11777908-Precipitin Tests,
pubmed-meshheading:11777908-Protein Binding,
pubmed-meshheading:11777908-Protein Isoforms,
pubmed-meshheading:11777908-RNA, Messenger,
pubmed-meshheading:11777908-Succinimides,
pubmed-meshheading:11777908-Tetradecanoylphorbol Acetate,
pubmed-meshheading:11777908-Time Factors,
pubmed-meshheading:11777908-Trypsin Inhibitor, Kunitz Soybean,
pubmed-meshheading:11777908-Tumor Cells, Cultured,
pubmed-meshheading:11777908-Up-Regulation,
pubmed-meshheading:11777908-Urokinase-Type Plasminogen Activator
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pubmed:year |
2002
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pubmed:articleTitle |
Kunitz-type protease inhibitor bikunin disrupts phorbol ester-induced oligomerization of CD44 variant isoforms containing epitope v9 and subsequently suppresses expression of urokinase-type plasminogen activator in human chondrosarcoma cells.
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pubmed:affiliation |
Department of Obstetrics and Gynecology, Hamamatsu University School of Medicine, Handacho 3600, Hamamatsu, Shizuoka, 431-3192, Japan.
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pubmed:publicationType |
Journal Article
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