論文 - 詳細
| RRC ID | 43969 |
|---|---|
| 著者 | Tamura H, Ishibashi M, Yamashita T, Tanosaki S, Okuyama N, Kondo A, Hyodo H, Shinya E, Takahashi H, Dong H, Tamada K, Chen L, Dan K, Ogata K. |
| タイトル | Marrow stromal cells induce B7-H1 expression on myeloma cells, generating aggressive characteristics in multiple myeloma. |
| ジャーナル | Leukemia |
| Abstract |
Tumor-associated B7-H1 molecules inhibit antitumor immunity in some malignancies. We found that B7-H1 expression on patient myeloma cells and human myeloma cell lines (HMCLs) was upregulated by cultivating the cells with autologous stromal cells and the human stromal cell line HS-5. Among major cytokines produced by HS-5 cells, interleukin (IL)-6-induced B7-H1 expression on HMCLs. Moreover, HS-5 cell-mediated B7-H1 expression was downregulated by inhibiting IL-6. B7-H1(+) HMCLs were more proliferative and less susceptible to antimyeloma chemotherapy compared with B7-H1(-) HMCLs. Moreover, the former cells showed higher levels of Bcl-2 and FasL expression than the latter. Finally, B7-H1 molecules on HMCLs induced T-cell apoptosis and anergy of tumor-specific T cells. Consistent with these in vitro observations, patients whose myeloma cells expressed high levels of B7-H1 had higher myeloma cell percentages in the bone marrow (BM) and higher serum lactate dehydrogenase levels compared with other myeloma patients. In addition, B7-H1 expression levels were often upregulated after myeloma patients relapsed or became refractory to therapy. Our data indicate that the BM microenvironment upregulates B7-H1 expression on myeloma cells, which links to the two biological actions of inducing T-cell downregulation and enhancing aggressive myeloma-cell characteristics. Modulating the B7-H1 pathway may be worthwhile in myeloma. |
| 巻・号 | 27(2) |
| ページ | 464-72 |
| 公開日 | 2013-2-1 |
| DOI | 10.1038/leu.2012.213 |
| PII | leu2012213 |
| PMID | 22828443 |
| MeSH | Apoptosis B7-H1 Antigen / genetics B7-H1 Antigen / metabolism* Blotting, Western Cell Proliferation Drug Resistance, Neoplasm* Fas Ligand Protein / genetics Fas Ligand Protein / metabolism Flow Cytometry Humans Interleukin-6 / genetics Interleukin-6 / metabolism Lymphocyte Activation Multiple Myeloma / drug therapy Multiple Myeloma / metabolism Multiple Myeloma / pathology* Neoplasm Recurrence, Local / drug therapy Neoplasm Recurrence, Local / metabolism Neoplasm Recurrence, Local / pathology* Proto-Oncogene Proteins c-bcl-2 / genetics Proto-Oncogene Proteins c-bcl-2 / metabolism RNA, Messenger / genetics Real-Time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction Stromal Cells / immunology Stromal Cells / metabolism Stromal Cells / pathology* T-Lymphocytes, Cytotoxic / immunology* Tumor Cells, Cultured |
| IF | 8.665 |
| 引用数 | 132 |
| WOS 分野 | ONCOLOGY HEMATOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 22 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 3.0 |
| リソース情報 | |
| ヒト・動物細胞 | PCM6(RCB1460) |