| 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
|
| リソース情報 |
| ヒト・動物細胞 |
LM8(RCB1450) |
