RRC ID |
62611
|
著者 |
Nishida J, Momoi Y, Miyakuni K, Tamura Y, Takahashi K, Koinuma D, Miyazono K, Ehata S.
|
タイトル |
Epigenetic remodelling shapes inflammatory renal cancer and neutrophil-dependent metastasis.
|
ジャーナル |
Nat Cell Biol
|
Abstract |
Advanced clear cell renal cell carcinoma (ccRCC) frequently causes systemic inflammation. Recent studies have shown that cancer cells reshape the immune landscape by secreting cytokines or chemokines. This phenotype, called cancer-cell-intrinsic inflammation, triggers a metastatic cascade. Here, we identified the functional role and regulatory mechanism of inflammation driven by advanced ccRCC cells. The inflammatory nature of advanced ccRCC was recapitulated in a preclinical model of ccRCC. Amplification of cancer-cell-intrinsic inflammation during ccRCC progression triggered neutrophil-dependent lung metastasis. Massive expression of inflammation-related genes was transcriptionally activated by epigenetic remodelling through mechanisms such as DNA demethylation and super-enhancer formation. A bromodomain and extra-terminal motif inhibitor synchronously suppressed C-X-C-type chemokines in ccRCC cells and decreased neutrophil-dependent lung metastasis. Overall, our findings provide insight into the nature of inflammatory ccRCC, which triggers metastatic cascades, and suggest a potential therapeutic strategy.
|
巻・号 |
22(4)
|
ページ |
465-475
|
公開日 |
2020-4-1
|
DOI |
10.1038/s41556-020-0491-2
|
PII |
10.1038/s41556-020-0491-2
|
PMID |
32203421
|
MeSH |
Animals
Carcinoma, Renal Cell / genetics*
Carcinoma, Renal Cell / metabolism
Carcinoma, Renal Cell / mortality
Carcinoma, Renal Cell / secondary
Cell Line, Tumor
Chemokines, CXC / genetics
Chemokines, CXC / metabolism
Disease Progression
Epigenesis, Genetic*
Gene Expression Profiling
Gene Expression Regulation, Neoplastic*
Humans
Inflammation
Kidney Neoplasms / genetics*
Kidney Neoplasms / metabolism
Kidney Neoplasms / mortality
Kidney Neoplasms / pathology
Lung Neoplasms / genetics*
Lung Neoplasms / metabolism
Lung Neoplasms / mortality
Lung Neoplasms / secondary
Lymphatic Metastasis
Male
Mice
Mice, Nude
Neoplasm Proteins / genetics*
Neoplasm Proteins / metabolism
Neutrophils / metabolism
Neutrophils / pathology
Prognosis
Survival Analysis
Tumor Microenvironment / genetics
Xenograft Model Antitumor Assays
|
IF |
20.042
|
リソース情報 |
遺伝子材料 |
CSII-EF-RfA (RDB04387)
pCMV-VSV-G-RSV-Rev (RDB04393)
pCAG-HIVgp (RDB04394) |
ヒト・動物細胞 |
OS-RC-2(RCB0735) |