The transient receptor potential vanilloid-2 cation channel impairs glioblastoma stem-like cell proliferation and promotes differentiation

Roberto Pallini, Luigi Maria Larocca, Ruggero De Maria Marchiano, Maria Beatrice Morelli, Massimo Nabissi, Consuelo Amantini, Valerio Farfariello, Lucia Ricci-Vitiani, Simona Di Martino, Sara Caprodossi, Matteo Santoni, Giorgio Santoni

Risultato della ricerca: Contributo in rivistaArticolo in rivista

49 Citazioni (Scopus)

Abstract

Malignant transformation of cells resulting from enhanced proliferation and aberrant differentiation is often accompanied by changes in transient receptor potential vanilloid (TRPV) channels expression. In gliomas, recent evidence indicates that TRPV type 2 (TRPV2) negatively controls glioma cell survival and proliferation. In addition, cannabinoids, the ligands of both cannabinoid and TRPV2 receptors, promote glioblastoma stem-like cells (GSCs) differentiation and inhibit gliomagenesis. Herein, we provide evidence on the expression of TRPV2 in human GSCs and that GSCs differentiation reduces nestin and progressively increases both the glial fibrillary acidic protein (GFAP) and TRPV2 expression. Therefore, we evaluated the role of TRPV2 cation channel in GSC lines differentiation. Treatment of GSC lines with the TRPV antagonist Ruthenium Red, with ethylene glycol-bis(2-aminoethylether)-N,N,N',N'-tetraacetic acid or knockdown of TRPV2 gene during differentiation, decreases GFAP and class III beta-tubulin (β III-tubulin) expression; conversely, phorbol-12-myristate-13-acetate stimulates GSCs proliferation, reduces TRPV2 expression and partially reverts astroglial differentiation. In addition, forced TRPV2 expression in GSC lines by stable TRPV2 transfection increases GFAP and β III-tubulin expression and parallelly reduces proliferation. Finally, TRPV2 overexpression inhibits GSCs proliferation in a xenograft mouse model, as shown by reduced tumor diameter and mitotic index, and promotes the differentiation of GSCs toward a more mature glial phenotype. Overall, our results demonstrate that TRPV2 promotes in vitro and in vivo GSCs differentiation and inhibits their proliferation. Better understanding of the molecular mechanisms that regulate the balance between proliferation and differentiation of GSCs would lead to more specific and efficacious pharmacological approaches. Copyright © 2012 UICC.
Lingua originaleEnglish
pagine (da-a)E1067-E1077
RivistaInternational Journal of Cancer
Volume131
DOI
Stato di pubblicazionePubblicato - 2012

Keywords

  • Animals
  • Calcium
  • Cancer Research
  • Cell Differentiation
  • Cell Line, Tumor
  • Cell Proliferation
  • Gene Expression
  • Glioblastoma
  • Humans
  • Mice
  • Mice, Nude
  • Neoplastic Stem Cells
  • Oncology
  • Phorbol Esters
  • TRP
  • TRPV Cation Channels
  • TRPV2
  • differentiation
  • glioblastoma
  • glioblastoma stem-like cells

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