| RRC ID |
52690
|
| 著者 |
Taki M, Abiko K, Baba T, Hamanishi J, Yamaguchi K, Murakami R, Yamanoi K, Horikawa N, Hosoe Y, Nakamura E, Sugiyama A, Mandai M, Konishi I, Matsumura N.
|
| タイトル |
Snail promotes ovarian cancer progression by recruiting myeloid-derived suppressor cells via CXCR2 ligand upregulation.
|
| ジャーナル |
Nat Commun
|
| Abstract |
Snail is a major transcriptional factor that induces epithelial-mesenchymal transition (EMT). In this study, we explore the effect of Snail on tumor immunity. Snail knockdown in mouse ovarian cancer cells suppresses tumor growth in immunocompetent mice, associated with an increase of CD8+ tumor-infiltrating lymphocytes and a decrease of myeloid-derived suppressor cells (MDSCs). Snail knockdown reduces the expression of CXCR2 ligands (CXCL1 and CXCL2), chemokines that attract MDSCs to the tumor via CXCR2. Snail upregulates CXCR ligands through NF-kB pathway, and most likely, through direct binding to the promoters. A CXCR2 antagonist suppresses MDSC infiltration and delays tumor growth in Snail-expressing mouse tumors. Ovarian cancer patients show elevated serum CXCL1/2, which correlates with Snail expression, MDSC infiltration, and short overall survival. Thus, Snail induces cancer progression via upregulation of CXCR2 ligands and recruitment of MDSCs. Blocking CXCR2 represents an immunological therapeutic approach to inhibit progression of Snail-high tumors undergoing EMT.
|
| 巻・号 |
9(1)
|
| ページ |
1685
|
| 公開日 |
2018-4-27
|
| DOI |
10.1038/s41467-018-03966-7
|
| PII |
10.1038/s41467-018-03966-7
|
| PMID |
29703902
|
| PMC |
PMC5923228
|
| MeSH |
Animals
Chemokine CXCL1 / blood
Chemokine CXCL1 / metabolism
Chemokine CXCL2 / blood
Chemokine CXCL2 / metabolism
Disease Progression
Epithelial-Mesenchymal Transition / genetics
Epithelial-Mesenchymal Transition / immunology
Female
Gene Expression Regulation, Neoplastic / immunology
Gene Knockdown Techniques
Humans
Mice
Mice, Inbred ICR
Mice, Nude
Middle Aged
Myeloid-Derived Suppressor Cells / immunology*
Ovarian Neoplasms / blood
Ovarian Neoplasms / genetics
Ovarian Neoplasms / immunology*
Ovarian Neoplasms / mortality
Receptors, Interleukin-8B / antagonists & inhibitors
Receptors, Interleukin-8B / immunology*
Receptors, Interleukin-8B / metabolism
Signal Transduction
Snail Family Transcription Factors / genetics
Snail Family Transcription Factors / metabolism*
Up-Regulation
Xenograft Model Antitumor Assays
|
| IF |
12.121
|
| 引用数 |
49
|
| リソース情報 |
| ヒト・動物細胞 |
OV2944-HM-1(RCB1483)
JHOS-2(RCB1521) |
