Document Detail


Killing tumor cells through their surface beta(2)-microglobulin or major histocompatibility complex class I molecules.
MedLine Citation:
PMID:  20143445     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Targeted antibody-based therapy has been used successfully to treat cancers. Recent studies have demonstrated that tumor cells treated with antibodies specific for beta(2)-microglobulin (beta(2)M) or major histocompatibility complex (MHC) class I molecules undergo apoptosis in vitro and in vivo (mouse models). Antibodies against beta(2)M or MHC class I induce tumor cell apoptosis by 1) recruiting MHC class I molecules to lipid rafts and activating LYN kinase and the signal-transducing enzyme phospholipase C-gamma2-dependent c-Jun N-terminal kinase signaling pathway and 2) expelling interleukin 6 and insulin-like growth factor 1 receptors out of lipid rafts and inhibiting the growth and survival factor-induced activation of the phosphatidylinositol 3-kinase/Akt and extracellular signal-related kinase pathways. Consequently, mitochondrial integrity is compromised, and the caspase-9-dependent cascade is activated in treated tumor cells. However, although beta(2)M and MHC class I are expressed on normal hematopoietic cells, which is a potential safety concern, the monoclonal antibodies were selective to tumor cells and did not damage normal cells in vitro or in human-like mouse models. These findings suggest that targeting beta(2)M or MHC class I by using antibodies or other agents offers a potential therapeutic approach for beta(2)M/MHC class I-expressing malignancies. Cancer 2010. (c) 2010 American Cancer Society.
Authors:
Jing Yang; Qing Yi
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review    
Journal Detail:
Title:  Cancer     Volume:  116     ISSN:  0008-543X     ISO Abbreviation:  Cancer     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-03-29     Completed Date:  2010-05-06     Revised Date:  2011-09-26    
Medline Journal Info:
Nlm Unique ID:  0374236     Medline TA:  Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1638-45     Citation Subset:  AIM; IM    
Affiliation:
Department of Lymphoma and Myeloma, Division of Cancer Medicine, Center for Cancer Immunology Research, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies, Monoclonal / therapeutic use
Apoptosis
Cell Line, Tumor
Drug Delivery Systems
Hematologic Neoplasms / drug therapy
Histocompatibility Antigens Class I
Membrane Microdomains / metabolism
Mice
Neoplasms / drug therapy*
Signal Transduction
beta 2-Microglobulin
Grant Support
ID/Acronym/Agency:
K99 CA137158-01A1/CA/NCI NIH HHS; K99/R00 CA137158/CA/NCI NIH HHS; R01 CA103978/CA/NCI NIH HHS; R01 CA138402/CA/NCI NIH HHS; R01 CA96569/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Histocompatibility Antigens Class I; 0/beta 2-Microglobulin
Comments/Corrections

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