論文 - 詳細
| RRC ID | 44110 |
|---|---|
| 著者 | Nishioka C, Ikezoe T, Furihata M, Yang J, Serada S, Naka T, Nobumoto A, Kataoka S, Tsuda M, Udaka K, Yokoyama A. |
| タイトル | CD34⁺/CD38⁻ acute myelogenous leukemia cells aberrantly express CD82 which regulates adhesion and survival of leukemia stem cells. |
| ジャーナル | Int J Cancer |
| 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. |
| 巻・号 | 132(9) |
| ページ | 2006-19 |
| 公開日 | 2013-5-1 |
| DOI | 10.1002/ijc.27904 |
| PMID | 23055153 |
| MeSH | ADP-ribosyl Cyclase 1 / genetics ADP-ribosyl Cyclase 1 / metabolism* Animals Antigens, CD34 / genetics Antigens, CD34 / metabolism* Blotting, Western Bone Marrow Transplantation Cell Adhesion Cell Movement Cell Proliferation Flow Cytometry Gene Expression Regulation, Neoplastic* Homeodomain Proteins / physiology Humans Immunoenzyme Techniques Kangai-1 Protein / antagonists & inhibitors Kangai-1 Protein / genetics Kangai-1 Protein / metabolism* Leukemia, Myeloid, Acute / genetics Leukemia, Myeloid, Acute / metabolism Leukemia, Myeloid, Acute / pathology* Matrix Metalloproteinase 2 / genetics Matrix Metalloproteinase 2 / metabolism Matrix Metalloproteinase 9 / genetics Matrix Metalloproteinase 9 / metabolism Mesenchymal Stem Cells / metabolism Mesenchymal Stem Cells / pathology Mice Mice, Inbred NOD Neoplastic Stem Cells / metabolism Neoplastic Stem Cells / pathology* Peptide Fragments / analysis RNA, Messenger / genetics RNA, Small Interfering / genetics Real-Time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Tumor Cells, Cultured |
| IF | 5.145 |
| 引用数 | 26 |
| WOS 分野 | ONCOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | EoL-1 cell(RCB0641) |