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, EGFR-expressing 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 EGFR(pos) and EGFR(neg) TIC subpopulations within the same tumor might affect clinical response to treatment.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Mazzoleni S,Politi LS,Pala M,Cominelli M,Franzin A,Sergi Sergi L,Falini A,De Palma M,Bulfone A,Poliani PL,Galli Rdoi
10.1158/0008-5472.CAN-10-2353subject
Has Abstractpub_date
2010-10-01 00:00:00pages
7500-13issue
19eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-10-2353journal_volume
70pub_type
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