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Updated: May 4, 2026
Quantitative Immunohistochemistry of the Cellular Microenvironment in Patient Glioblastoma Resections
Published on: July 31, 2017
Sustained elevation of Snail promotes glial-mesenchymal transition after irradiation in malignant glioma
Roshan Mahabir1, Mishie Tanino, Aiman Elmansuri
1Department of Cancer Pathology, Hokkaido University Graduate School of Medicine, Sapporo, Japan (R.M., M.T., A.E., T.K., M.T., S.T.); Department of Translational Pathology, Hokkaido University Graduate School of Medicine, Sapporo, Japan (L.W., H.N., S.T.); Department of Cell Physiology, Hokkaido University Graduate School of Medicine, Sapporo, Japan (Y.O.); Department of Radiology, Hokkaido University Graduate School of Medicine, Sapporo, Japan (H.S.); Department of Neurosurgery, Nakamura Memorial Hospital, Sapporo, Japan (T.I).
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.
