title: Tumor-initiating cell frequency is relevant for glioblastoma aggressiveness.
abstract: Glioblastoma (GBM) is maintained by a small subpopulation of tumor-initiating cells (TICs). The arduous assessment of TIC frequencies challenges the prognostic role of TICs in predicting the clinical outcome in GBM patients. We estimated the TIC frequency in human GBM injecting intracerebrally in mice dissociated cells without any passage in culture.All GBMs contained rare TICsand were tumorigenic in vivo but only 54% of them grew in vitro as neurospheres. We demonstrated that neurosphere formation in vitro did not foretell tumorigenic ability in vivo and frequencies calculated in vitro overestimated the TIC content.Our findings assert the pathological significance of GBM TICs. TIC number correlated positively with tumor incidence and inversely with survival of tumor-bearing mice. Stratification of GBM patients according to TIC content revealed that patients with low TIC frequency experienced a trend towards a longer progression free survival. The expression of either putative stem-cell markers or markers associated with different GBM molecular subtypes did not associate with either TIC content or neurosphere formation underlying the limitations of TIC identification based on the expression of some putative stem cell-markers.
authors: Department of Experimental Oncology, European Institute of Oncology, 20139, Milan, Italy.
authors: Cristina
authors: C
authors: Richichi
authors: Department of Experimental Oncology, European Institute of Oncology, 20139, Milan, Italy.
authors: Daniela
authors: D
authors: Osti
authors: Department of Neurosurgery, IRCCS Foundation Neurological Institute "C. Besta", 20133, Milan, Italy.
authors: Massimiliano
authors: M
authors: Del Bene
authors: Department of Experimental Oncology, European Institute of Oncology, 20139, Milan, Italy.
authors: Lorenzo
authors: L
authors: Fornasari
authors: Department of Neuropathology, IRCCS Foundation Neurological Institute "C. Besta", 20133, Milan, Italy.
authors: Monica
authors: M
authors: Patanè
authors: Department of Neuropathology, IRCCS Foundation Neurological Institute "C. Besta", 20133, Milan, Italy.
authors: Bianca
authors: B
authors: Pollo
authors: Department of Neurosurgery, IRCCS Foundation Neurological Institute "C. Besta", 20133, Milan, Italy.|Department of Neurosurgery, Johns Hopkins University, Baltimore, MD 21218, USA.
authors: Francesco
authors: F
authors: DiMeco
authors: Department of Experimental Oncology, European Institute of Oncology, 20139, Milan, Italy.|Department of Translational Medicine, Piemonte Orientale University "Amedeo Avogadro", 28100 Novara, Italy.
authors: Giuliana
authors: G
authors: Pelicci
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001932:Brain Neoplasms / Q000401:mortality / Q000473:pathology*; D005260:Female; D005909:Glioblastoma / Q000401:mortality / Q000473:pathology*; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000473:pathology*
keywords: glioblastoma; limiting dilution assay; neurosphere; tumor-initiating cell frequency; tumorigenicity