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 language | English |
|---|---|
| Pages (from-to) | 7500-7513 |
| Number of pages | 14 |
| Journal | Cancer Research |
| Volume | 70 |
| Issue number | 19 |
| DOIs | |
| Publication status | Published - Oct 1 2010 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
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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 journal › Article
}
TY - JOUR
T1 - Epidermal growth factor receptor expression identifies functionally and molecularly distinct tumor-initiating cells in human glioblastoma multiforme and is required for gliomagenesis
AU - Mazzoleni, Stefania
AU - Politi, Letterio S.
AU - Pala, Mauro
AU - Cominelli, Manuela
AU - Franzin, Alberto
AU - Sergi, Lucia Sergi
AU - Falini, Andrea
AU - De Palma, Michele
AU - Bulfone, Alessandro
AU - Poliani, Pietro L.
AU - Galli, Rossella
PY - 2010/10/1
Y1 - 2010/10/1
N2 - 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.
AB - 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.
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U2 - 10.1158/0008-5472.CAN-10-2353
DO - 10.1158/0008-5472.CAN-10-2353
M3 - Article
VL - 70
SP - 7500
EP - 7513
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0008-5472
IS - 19
ER -