| 著者 |
Nishioka C, Ikezoe T, Furihata M, Yang J, Serada S, Naka T, Nobumoto A, Kataoka S, Tsuda M, Udaka K, Yokoyama A.
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| 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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