論文 - 詳細
| RRC ID | 51839 |
|---|---|
| 著者 | Kanzaki H, Shinohara F, Suzuki M, Wada S, Miyamoto Y, Yamaguchi Y, Katsumata Y, Makihira S, Kawai T, Taubman MA, Nakamura Y. |
| タイトル | A-Disintegrin and Metalloproteinase (ADAM) 17 Enzymatically Degrades Interferon-gamma. |
| ジャーナル | Sci Rep |
| Abstract |
Interferon-gamma (IFN-γ) is a pleiotropic cytokine that exerts anti-tumor and anti-osteoclastogenic effects. Although transcriptional and post-transcriptional regulation of IFN-γ is well understood, subsequent modifications of secreted IFN-γ are not fully elucidated. Previous research indicates that some cancer cells escape immune surveillance and metastasize into bone tissue by inducing osteoclastic bone resorption. Peptidases of the a-disintegrin and metalloproteinase (ADAM) family are implicated in cancer cell proliferation and tumor progression. We hypothesized that the ADAM enzymes expressed by cancer cells degrades IFN-γ and attenuates IFN-γ-mediated anti-tumorigenic and anti-osteoclastogenic effects. Recombinant ADAM17 degraded IFN-γ into small fragments. The addition of ADAM17 to the culture supernatant of stimulated mouse splenocytes decreased IFN-γ concentration. However, ADAM17 inhibition in the stimulated mouse T-cells prevented IFN-γ degradation. ADAM17-expressing human breast cancer cell lines MCF-7 and MDA-MB-453 also degraded recombinant IFN-γ, but this was attenuated by ADAM17 inhibition. Degraded IFN-γ lost the functionality including the inhibititory effect on osteoclastogenesis. This is the first study to demonstrate the extracellular proteolytic degradation of IFN-γ by ADAM17. These results suggest that ADAM17-mediated degradation of IFN-γ may block the anti-tumorigenic and anti-osteoclastogenic effects of IFN-γ. ADAM17 inhibition may be useful for the treatment of attenuated cancer immune surveillance and/or bone metastases. |
| 巻・号 | 6 |
| ページ | 32259 |
| 公開日 | 2016-8-30 |
| DOI | 10.1038/srep32259 |
| PII | srep32259 |
| PMID | 27573075 |
| PMC | PMC5004192 |
| MeSH | ADAM17 Protein / genetics ADAM17 Protein / immunology ADAM17 Protein / metabolism* Amino Acid Sequence Animals Antibodies, Monoclonal / immunology Antibodies, Monoclonal / pharmacology Antibodies, Neutralizing / immunology Antibodies, Neutralizing / pharmacology Breast Neoplasms / genetics Breast Neoplasms / metabolism Breast Neoplasms / pathology Cell Line, Tumor Cells, Cultured Humans Interferon-gamma / genetics Interferon-gamma / metabolism* MCF-7 Cells Mice Mice, Inbred BALB C Proteolysis / drug effects RAW 264.7 Cells RNA Interference Recombinant Proteins / metabolism* T-Lymphocytes / drug effects T-Lymphocytes / metabolism* |
| IF | 3.998 |
| 引用数 | 5 |
| 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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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | MCF7(RCB1904) MDA-MB-453(RCB1192) RAW 264(RCB0535) |