Source:http://linkedlifedata.com/resource/pubmed/id/19748980
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
7
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| pubmed:dateCreated |
2009-9-21
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| pubmed:abstractText |
Modulation of the host immune system represents a promising therapeutic approach against cancer, including multiple myeloma. Recent findings indicate that the NK group 2D (NKG2D)- and DNAX accessory molecule-1 (DNAM-1)-activating receptors play a prominent role in tumor recognition and elimination by cytotoxic lymphocytes, suggesting that the levels of NKG2D and DNAM-1 ligand expression on tumor cells may be a critical factor to improve the immune response against cancer. In this study, we tested the effect of 17-allylaminogeldanamycin and radicicol, drugs targeting the heat shock protein-90 (HSP-90) chaperone protein and displaying antimyeloma activity, on the expression of NKG2D and DNAM-1 ligands in human myeloma cell lines. We demonstrate that HSP-90 inhibitors are able to up-regulate both MHC class I chain-related (MIC) A and MICB protein surface and mRNA expression in human myeloma cell lines, without any significant effect on the basal expression of the DNAM-1 ligand poliovirus receptor CD155, or induction of nectin-2 and UL16-binding proteins. Activation of the transcription factor heat shock factor-1 by HSP-90 inhibitors is essential for the up-regulation of MICA/MICB expression and knockdown of heat shock factor-1 using small hairpin RNA interference blocks this effect. Moreover, in vitro and in vivo binding of heat shock factor-1 to MICA and MICB promoters indicates that it may enhance NKG2D ligand expression at the transcriptional level. Finally, exposure to HSP-90 inhibitors renders myeloma cells more efficient to activate NK cell degranulation and a blocking Ab specific for NKG2D significantly reduces this effect. Thus, these results provide evidence that targeting NKG2D ligands expression may be an additional mechanism supporting the antimyeloma activity of HSP-90 inhibitors and suggest their possible immunotherapeutic value.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/17-(allylamino)-17-demethoxygeldanam...,
http://linkedlifedata.com/resource/pubmed/chemical/Benzoquinones,
http://linkedlifedata.com/resource/pubmed/chemical/Boronic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/GPI-Linked Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/HSP90 Heat-Shock Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Histocompatibility Antigens Class I,
http://linkedlifedata.com/resource/pubmed/chemical/Intercellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Lactams, Macrocyclic,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/MHC class I-related chain A,
http://linkedlifedata.com/resource/pubmed/chemical/MICB antigen,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrazines,
http://linkedlifedata.com/resource/pubmed/chemical/ULBP2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/bortezomib
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| pubmed:status |
MEDLINE
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| pubmed:month |
Oct
|
| pubmed:issn |
1550-6606
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:day |
1
|
| pubmed:volume |
183
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
4385-94
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| pubmed:dateRevised |
2010-11-18
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| pubmed:meshHeading |
pubmed-meshheading:19748980-Benzoquinones,
pubmed-meshheading:19748980-Boronic Acids,
pubmed-meshheading:19748980-Cell Degranulation,
pubmed-meshheading:19748980-Cell Line, Tumor,
pubmed-meshheading:19748980-GPI-Linked Proteins,
pubmed-meshheading:19748980-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:19748980-HSP90 Heat-Shock Proteins,
pubmed-meshheading:19748980-Histocompatibility Antigens Class I,
pubmed-meshheading:19748980-Humans,
pubmed-meshheading:19748980-Intercellular Signaling Peptides and Proteins,
pubmed-meshheading:19748980-Killer Cells, Natural,
pubmed-meshheading:19748980-Lactams, Macrocyclic,
pubmed-meshheading:19748980-Ligands,
pubmed-meshheading:19748980-Multiple Myeloma,
pubmed-meshheading:19748980-Protein Folding,
pubmed-meshheading:19748980-Pyrazines,
pubmed-meshheading:19748980-Up-Regulation
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| pubmed:year |
2009
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| pubmed:articleTitle |
Heat shock protein-90 inhibitors increase MHC class I-related chain A and B ligand expression on multiple myeloma cells and their ability to trigger NK cell degranulation.
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| pubmed:affiliation |
Department of Experimental Medicine, Istituto Pasteur-Fondazione Cenci Bolognetti, University of Rome Sapienza, Rome, Italy.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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