Linked Life Data

19056691

Source:http://linkedlifedata.com/resource/pubmed/id/19056691

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2009-3-13
pubmed:abstractText
Down-regulation of conventional human leukocyte antigen (HLA) class I and II molecules from the surface of tumor cells is an important mechanism for tumor immune evasion, survival, and progression. Whether CD1d, a nonconventional, glycolipid-presenting HLA class I-like molecule instructing the function of the immunoregulatory invariant NKT cells can affect tumor cell survival is not known. Here we show that CD1d is highly expressed in premalignant and early myeloma, but with disease progression its expression is reduced and eventually in advanced stages and myeloma cell lines is lost altogether, suggesting that CD1d impacts negatively on myeloma cell survival. Consistent with this, engagement of CD1d by anti-CD1d monoclonal antibodies (mAbs) induces cell death of myeloma cell lines with restored CD1d expression and primary myeloma cells. Cell death induced by monoclonal antibody engagement of CD1d is associated with overexpression of proapoptotic Bax and mitochondrial membrane potential loss but it is caspase-activation independent; in addition, it requires the cytoplasmic tail but not the Tyr residue critical for lysosomal sorting of CD1d. Finally, anti-CD1d cooperates with antimyeloma agents in the killing of myeloma cells. Thus, this work provides evidence linking a novel function of CD1d in the regulation of cell death with tumor survival and progression in humans.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1528-0020
pubmed:author
pubmed:issnType
Electronic
pubmed:day
12
pubmed:volume
113
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2498-507
pubmed:meshHeading
pubmed-meshheading:19056691-Antibodies, Monoclonal, pubmed-meshheading:19056691-Antigens, CD1d, pubmed-meshheading:19056691-Antineoplastic Combined Chemotherapy Protocols, pubmed-meshheading:19056691-Apoptosis, pubmed-meshheading:19056691-B-Lymphocytes, pubmed-meshheading:19056691-Boronic Acids, pubmed-meshheading:19056691-Cell Aggregation, pubmed-meshheading:19056691-Cell Survival, pubmed-meshheading:19056691-Dexamethasone, pubmed-meshheading:19056691-Disease Progression, pubmed-meshheading:19056691-Drug Evaluation, Preclinical, pubmed-meshheading:19056691-Gene Expression Regulation, Neoplastic, pubmed-meshheading:19056691-Humans, pubmed-meshheading:19056691-Multiple Myeloma, pubmed-meshheading:19056691-Plasma Cells, pubmed-meshheading:19056691-Pyrazines, pubmed-meshheading:19056691-Tumor Cells, Cultured
pubmed:year
2009
pubmed:articleTitle
Regulation of multiple myeloma survival and progression by CD1d.
pubmed:affiliation
Department of Haematology, Imperial College Healthcare National Health Service (NHS) Trust, Hammersmith and St Mary's Hospital, Imperial College London, London, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't