Epidermal growth factor receptor expression identifies functionally and molecularly distinct tumor-initiating cells in human glioblastoma multiforme and is required for gliomagenesis

Stefania Mazzoleni, Letterio S. Politi, Mauro Pala, Manuela Cominelli, Alberto Franzin, Lucia Sergi Sergi, Andrea Falini, Michele De Palma, Alessandro Bulfone, Pietro L. Poliani, Rossella Galli

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122 Citations (Scopus)

Abstract

Epidermal growth factor receptor (EGFR) is a known diagnostic and, although controversial, prognostic marker of human glioblastoma multiforme (GBM). However, its functional role and biological significance in GBM remain elusive. Here, we show that multiple GBM cell subpopulations could be purified from the specimens of patients with GBM and from cancer stem cell (CSC) lines based on the expression of EGFR and of other putative CSC markers. All these subpopulations are molecularly and functionally distinct, are tumorigenic, and need to express EGFR to promote experimental tumorigenesis. Among them, EGFRexpressing tumor-initiating cells (TIC) display the most malignant functional and molecular phenotype. Accordingly, modulation of EGFR expression by gain-of-function and loss-of-function strategies in GBM CSC lines enhances and reduces their tumorigenic ability, respectively, suggesting that EGFR plays a fundamental role in gliomagenesis. These findings open up the possibility of new therapeutically relevant scenarios, as the presence of functionally heterogeneous EGFRpos and EGFRneg TIC subpopulations within the same tumor might affect clinical response to treatment.

Original languageEnglish
Pages (from-to)7500-7513
Number of pages14
JournalCancer Research
Volume70
Issue number19
DOIs
Publication statusPublished - Oct 1 2010

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Neoplastic Stem Cells
Glioblastoma
Epidermal Growth Factor Receptor
Cell Line
Carcinogenesis
Phenotype
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Epidermal growth factor receptor expression identifies functionally and molecularly distinct tumor-initiating cells in human glioblastoma multiforme and is required for gliomagenesis. / Mazzoleni, Stefania; Politi, Letterio S.; Pala, Mauro; Cominelli, Manuela; Franzin, Alberto; Sergi, Lucia Sergi; Falini, Andrea; De Palma, Michele; Bulfone, Alessandro; Poliani, Pietro L.; Galli, Rossella.

In: Cancer Research, Vol. 70, No. 19, 01.10.2010, p. 7500-7513.

Research output: Contribution to journalArticle

Mazzoleni, Stefania ; Politi, Letterio S. ; Pala, Mauro ; Cominelli, Manuela ; Franzin, Alberto ; Sergi, Lucia Sergi ; Falini, Andrea ; De Palma, Michele ; Bulfone, Alessandro ; Poliani, Pietro L. ; Galli, Rossella. / Epidermal growth factor receptor expression identifies functionally and molecularly distinct tumor-initiating cells in human glioblastoma multiforme and is required for gliomagenesis. In: Cancer Research. 2010 ; Vol. 70, No. 19. pp. 7500-7513.
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