CD34âº/CD38â» acute myelogenous leukemia cells aberrantly express CD82 which regulates adhesion and survival of leukemia stem cells.
Int J Cancer
; 132(9): 2006-19, 2013 May 01.
Article
em En
| MEDLINE
| ID: mdl-23055153
ABSTRACT
To identify molecular targets in leukemia stem cells (LSCs), this study compared the protein expression profile of freshly isolated CD34(+) /CD38(-) cells with that of CD34(+) /CD38(+) counterparts from individuals with acute myelogenous leukemia (n = 2, AML) using isobaric tags for relative and absolute quantitation (iTRAQ). A total of 98 proteins were overexpressed, while six proteins were underexpressed in CD34(+) /CD38(-) AML cells compared with their CD34(+) /CD38(+) counterparts. Proteins overexpressed in CD34(+) /CD38(-) AML cells included a number of proteins involved in DNA repair, cell cycle arrest, gland differentiation, antiapoptosis, adhesion, and drug resistance. Aberrant expression of CD82, a family of adhesion molecules, in CD34(+) /CD38(-) AML cells was noted in additional clinical samples (n = 12) by flow cytometry. Importantly, down-regulation of CD82 in CD34(+) /CD38(-) AML cells by a short hairpin RNA (shRNA) inhibited adhesion to fibronectin via up-regulation of matrix metalloproteinases 9 (MMP9) and colony forming ability of these cells as assessed by transwell assay, real-time RT-PCR, and colony forming assay, respectively. Moreover, we found that down-regulation of CD82 in CD34(+) /CD38(-) AML cells by an shRNA significantly impaired engraftment of these cells in severely immunocompromised mice. Taken together, aberrant expression of CD82 might play a role in adhesion of LSCs to bone marrow microenvironment and survival of LSCs. CD82 could be an attractive molecular target to eradicate LSCs.
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1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco Neoplásicas
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Leucemia Mieloide Aguda
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Regulação Neoplásica da Expressão Gênica
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Antígenos CD34
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ADP-Ribosil Ciclase 1
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Proteína Kangai-1
Idioma:
En
Revista:
Int J Cancer
Ano de publicação:
2013
Tipo de documento:
Article