論文 - 詳細
| RRC ID | 66114 |
|---|---|
| 著者 | Yamazaki S, Ohka F, Hirano M, Shiraki Y, Motomura K, Tanahashi K, Tsujiuchi T, Motomura A, Aoki K, Shinjo K, Murofushi Y, Kitano Y, Maeda S, Kato A, Shimizu H, Yamaguchi J, Adilijiang A, Wakabayashi T, Saito R, Enomoto A, Kondo Y, Natsume A. |
| タイトル | Newly established patient-derived organoid model of intracranial meningioma. |
| ジャーナル | Neuro Oncol |
| Abstract |
BACKGROUND:Recent comprehensive studies have revealed several molecular alterations that are frequently found in meningiomas. However, effective treatment reagents targeting specific molecular alterations have not yet been identified because of the limited number of representative research models of meningiomas. METHODS:We performed organoid cultures using meningioma cells and meningioma tumor tissues. Using immunohistochemistry and molecular analyses consisting of whole exome sequencing, RNA-seq, and DNA methylation analyses, we compared the histological findings and molecular profiling of organoid models with those of parental tumors. Further, using these organoid models together with a public database of meningiomas, we explored molecular alterations, which are a potent treatment target for meningioma. RESULTS:We established 18 organoid models comprising of two malignant meningioma cells (HKBMM and IOMM-Lee), 10 benign meningiomas, four malignant meningiomas, and two solitary fibrous tumors (SFTs). The organoids exhibited consistent histological features and molecular profiles with those of the parental tumors. Using a public database, we identified that upregulated forkhead box M1 (FOXM1) was correlated with increased tumor proliferation. Overexpression of FOXM1 in benign meningioma organoids increased organoid proliferation; depletion of FOXM1 in malignant organoids decreased proliferation. Additionally, thiostrepton, a FOXM1 inhibitor combined with radiation therapy, significantly inhibited proliferation of malignant meningioma organoid models. CONCLUSIONS:An organoid model for meningioma enabled us to elucidate the tumor biology of meningioma along with potent treatment targets for meningioma. |
| 巻・号 | 23(11) |
| ページ | 1936-1948 |
| 公開日 | 2021-11-2 |
| DOI | 10.1093/neuonc/noab155 |
| PII | 6313216 |
| PMID | 34214169 |
| PMC | PMC8563327 |
| MeSH | Forkhead Box Protein M1 / genetics* Humans Meningeal Neoplasms* / genetics Meningioma* / genetics Organoids |
| IF | 10.247 |
| リソース情報 | |
| ヒト・動物細胞 | HKBMM(RCB0680) |