Sustained elevation of Snail promotes glial-mesenchymal transition after irradiation in malignant glioma
| العنوان: | Sustained elevation of Snail promotes glial-mesenchymal transition after irradiation in malignant glioma |
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| المؤلفون: | Masumi Tsuda, Hiroshi Nishihara, Tamio Itoh, Hiroki Shirato, Lei Wang, Mishie Tanino, Roshan Mahabir, Taichi Kimura, Shinya Tanaka, Yusuke Ohba, Aiman Elmansuri |
| المصدر: | Neuro-Oncology. 16:671-685 |
| بيانات النشر: | Oxford University Press (OUP), 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Cancer Research, Pathology, medicine.medical_specialty, Epithelial-Mesenchymal Transition, Vimentin, Mice, SOX2, Cell Line, Tumor, Glioma, medicine, Animals, Humans, Epithelial–mesenchymal transition, biology, Brain Neoplasms, CD44, Mesenchymal stem cell, medicine.disease, Mice, Mutant Strains, Oncology, Cell culture, Tumor progression, Basic and Translational Investigations, Disease Progression, biology.protein, Cancer research, Female, Snail Family Transcription Factors, Neurology (clinical), Signal Transduction, Transcription Factors |
| الوصف: | Background Ionizing irradiation is an effective treatment for malignant glioma (MG); however, a higher rate of recurrence with more aggressive phenotypes is a vital issue. Although epithelial-mesenchymal transition (EMT) is involved in irradiation-induced cancer progression, the role for such phenotypic transition in MG remains unknown. Methods To investigate the mechanism of irradiation-dependent tumor progression in MG, we performed immunohistochemistry (IHC) and qRT-PCR using primary and recurrent MG specimens, MG cell lines, and primary culture cells of MG. siRNA technique was used for MG cell lines. Results In 22 cases of clinically recurrent MG, the expression of the mesenchymal markers vimentin and CD44 was found to be increased by IHC. In paired identical MG of 7 patients, the expression of collagen, MMPs, and YKL-40 were also elevated in the recurrent MGs, suggesting the The Cancer Genome Atlas-based mesenchymal subtype. Among EMT regulators, sustained elevation of Snail was observed in MG cells at 21 days after irradiation. Cells exhibited an upregulation of migration, invasion, numbers of focal adhesion, and MMP-2 production, and all of these mesenchymal features were abrogated by Snail knockdown. Intriguingly, phosphorylation of ERK1/2 and GSK-3β were increased after irradiation in a Snail-dependent manner, and TGF-β was elevated in both fibroblasts and macrophages but not in MG cells after irradiation. It was noteworthy that irradiated cells also expressed stemness features such as SOX2 expression and tumor-forming potential in vivo. Conclusions We here propose a novel concept of glial-mesenchymal transition after irradiation in which the sustained Snail expression plays an essential role. |
| تدمد: | 1523-5866 1522-8517 |
| DOI: | 10.1093/neuonc/not239 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::96e1864bbd850401a50952cd73f727cf https://doi.org/10.1093/neuonc/not239 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....96e1864bbd850401a50952cd73f727cf |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15235866 15228517 |
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| DOI: | 10.1093/neuonc/not239 |