Abstract
Novel data report a “cross-talk” between Heat-Shock Factor 1 (HSF1) and the transient receptor potential vanilloid 1 cation channel (TRPV1) located in the cell membrane, introducing these channels as possible drug targets for the regulation of HSF1 activation. This study aims to investigate the co-expression of TRPV1 and HSF1 in human brain tumors. Additionally, the expression of the transient receptor potential ankyrin 1 channel (TRPA1), which is co-operated with TRPV1 in a plethora of cells, was studied. Immunohistochemical staining for HSF1, TRPV1 and TRPA1 expression was quantitatively analyzed in paraffin-embedded semi-serial tissue sections from 74 gliomas and 71 meningiomas. mRNA levels of HSF1, TRPV1 and TRPA1 were evaluated using real-time PCR. Although HSF1 was significantly increased compared with TRPV1/TRPA1 (p ≤ 0.001) in both gliomas and meningiomas, high co-expression levels for HSF1, TRPV1 and TRPA1 were found in 62.50% of diffuse fibrillary astrocytomas (WHO, grade II), 37.50% of anaplastic astrocytomas (WHO, grade III), 16.32% of glioblastomas multiforme (WHO, grade IV), and 42.25% of meningiomas (WHO, grade I and II). Correlation analysis revealed a relationship of HSF1 with TRPV1/TRPA1 in diffuse fibrillary astrocytomas (WHO, grade II) and benign meningiomas (WHO, grade I) contrary to glioblastomas multiforme (WHO, grade IV) and high grade meningiomas (WHO, grade II). Importantly, TRPA1 and TRPV1 expression levels were significantly increased in meningiomas compared with astrocytic tumors (p < 0.05). In conclusion, HSF1 and TRPV1/TRPA1 co-expression may be implicated in the pathogenesis of human brain tumors and should be considered for the therapeutic approaches for these tumors.
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The datasets used and/or analyzed and materials from the current study are available from the corresponding author on reasonable request.
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Acknowledgements
The authors appreciate the valuable help of Maria-Elpida Christopoulou PhD, Laboratory of Biochemistry, Department of Chemistry, University of Patras, 26504, Patras, Greece for the presentation of real-time PCR results.
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MA conceived, designed, and supervised the whole study, performed the analysis of immunohistochemical and statistical findings, and wrote the manuscript. AM performed the experiments and analyzed the data. GG provided clinical information of the patients. VZ carried out the pathological evaluation of the specimens. All authors revised and approved the manuscript.
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The use of archival material and clinical information of the patients was approved by the University Ethics Commission according to the principles of the Declaration of Helsinki (as revised in Edinburgh 2000). This study was considered of minimal risk to patients. All patients were informed and consent. All ethical guidelines and rules were followed to protect patient privacy.
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Moutafidi, A., Gatzounis, G., Zolota, V. et al. Heat shock factor 1 in brain tumors: a link with transient receptor potential channels TRPV1 and TRPA1. J Mol Histol 52, 1233–1244 (2021). https://doi.org/10.1007/s10735-021-10025-x
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DOI: https://doi.org/10.1007/s10735-021-10025-x