論文 - 詳細
| RRC ID | 85690 |
|---|---|
| 著者 | Pan C, Fujiwara Y, Horlad H, Iriki T, Shiraishi D, Komohara Y. |
| タイトル | Cyclic sulfur compounds targeting macrophage polarization into M2/protumor phenotype and their anti-tumor effects. |
| ジャーナル | Cancer Immunol Immunother |
| Abstract |
Tumor-associated macrophages (TAMs), especially the M2-like phenotype, promote tumor progression, making them candidate targets for anti-tumor therapy. We previously discovered a cyclic sulfur compound, Onionin A (ONA), which suppresses tumor progression by inhibiting the M2-polarization of TAMs. In the present study, we sought to find new candidate compounds possessing a stronger effect compared to ONA by exploring compounds with structures similar to those of ONA among several cyclic sulfur compounds. A total of 81 cyclic sulfur compounds were screened, and their effects on macrophage polarization toward an M2-like phenotype were tested using human monocyte-derived macrophages (HMDMs). The anti-tumor effects of the identified candidate compounds were examined in a tumor-bearing mouse model. Three candidate compounds inhibited both IL-10- and tumor culture supernatant (TCS)-induced M2-polarization of HMDMs. These compounds also suppressed STAT3 activation in HMDMs stimulated by IL-10 and TCS, whereas these compounds had no effect on STAT3 activation in tumor cells. Furthermore, these compounds inhibited tumor cell proliferation under co-culture conditions with HMDMs, indicating that the three candidate compounds suppress tumor proliferation by regulating cell-cell interactions between tumor cells and macrophages. In addition, two of these candidate compounds had inhibitory effects on tumor growth and lung metastasis in the LM8 tumor-bearing mouse model. Our study identified new candidate cyclic sulfur compounds for anti-tumor therapy targeting the M2-polarization of TAMs. |
| 巻・号 | 71(6) |
| ページ | 1331-1343 |
| 公開日 | 2022-6-1 |
| DOI | 10.1007/s00262-021-03085-1 |
| PII | 10.1007/s00262-021-03085-1 |
| PMID | 34655303 |
| PMC | PMC10991883 |
| MeSH | Animals Cell Line, Tumor Humans Interleukin-10* / pharmacology Macrophage Activation Macrophages Mice Phenotype Sulfur Compounds* / pharmacology Tumor Microenvironment |
| IF | 5.442 |
| 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 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | LM8(RCB1450) |