Heat shock factor 1 in brain tumors: a link with transient receptor potential channels TRPV1 and TRPA1

J Mol Histol. 2021 Dec;52(6):1233-1244. doi: 10.1007/s10735-021-10025-x. Epub 2021 Sep 30.

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.

Keywords: Brain tumors; Gliomas; HSF1; Meningiomas; TRPA1; TRPV1.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers
  • Brain Neoplasms / diagnosis
  • Brain Neoplasms / etiology*
  • Brain Neoplasms / metabolism*
  • Case-Control Studies
  • Disease Susceptibility*
  • Female
  • Gene Expression
  • Glioma
  • Heat Shock Transcription Factors / genetics*
  • Heat Shock Transcription Factors / metabolism
  • Humans
  • Immunohistochemistry
  • Male
  • Meningioma
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Organ Specificity
  • Prognosis
  • Protein Binding
  • Signal Transduction
  • TRPA1 Cation Channel / metabolism*
  • TRPV Cation Channels / metabolism*

Substances

  • Biomarkers
  • HSF1 protein, human
  • Heat Shock Transcription Factors
  • TRPA1 Cation Channel
  • TRPA1 protein, human
  • TRPV Cation Channels
  • TRPV1 protein, human