1. Newly established patient-derived organoid model of intracranial meningioma
- Author
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Shintaro Yamazaki, Fumiharu Ohka, Yotaro Kitano, Kosuke Aoki, Yutaka Kondo, Takashi Tsujiuchi, Hiroyuki Shimizu, Alimu Adilijiang, Kuniaki Tanahashi, Yukihiro Shiraki, Toshihiko Wakabayashi, Kazuya Motomura, Atsushi Enomoto, Akira Kato, Ryuta Saito, Sachi Maeda, Atsushi Natsume, Masaki Hirano, Ayako Motomura, Keiko Shinjo, Junya Yamaguchi, and Yoshiteru Murofushi
- Subjects
Cancer Research ,Solitary fibrous tumor ,Malignant meningioma ,medicine.medical_treatment ,Forkhead Box Protein M1 ,Biology ,medicine.disease ,nervous system diseases ,Organoids ,Radiation therapy ,Meningioma ,Oncology ,Basic and Translational Investigations ,Benign Meningioma ,Meningeal Neoplasms ,otorhinolaryngologic diseases ,medicine ,Organoid ,FOXM1 ,Cancer research ,Humans ,Immunohistochemistry ,Neurology (clinical) ,neoplasms - 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 the 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.
- Published
- 2021
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