TY - JOUR
T1 - Progenitor/stem cell markers in brain adjacent to glioblastoma
T2 - GD3 ganglioside and NG2 proteoglycan expression
AU - Lama, Gina
AU - Mangiola, Annunziato
AU - Proietti, Gabriella
AU - Colabianchi, Anna
AU - Angelucci, Cristiana
AU - D'Alessio, Alessio
AU - De Bonis, Pasquale
AU - Geloso, Maria Concetta
AU - Lauriola, Libero
AU - Binda, Elena
AU - Biamonte, Filippo
AU - Giuffrida, Maria Grazia
AU - Vescovi, Angelo
AU - Sica, Gigliola
N1 - Publisher Copyright:
© 2016 American Association of Neuropathologists, Inc. All rights reserved.
PY - 2016/2
Y1 - 2016/2
N2 - Characterization of tissue surrounding glioblastoma (GBM) is a focus for translational research because tumor recurrence invariably occurs in this area. We investigated the expression of the progenitor/ stem cell markers GD3 ganglioside and NG2 proteoglycan in GBM, peritumor tissue (brain adjacent to tumor, BAT) and cancer stem-like cells (CSCs) isolated from GBM (GCSCs) and BAT (PCSCs). GD3 and NG2 immunohistochemistry was performed in paired GBM and BAT specimens from 40 patients. Double-immunofluorescence was carried out to characterize NG2-positive cells of vessel walls. GD3 and NG2 expression was investigated in GCSCs and PCSCs whose tumorigenicity was also evaluated in Scid/bg mice. GD3 and NG2 expression was higher in tumor tissue than in BAT. NG2 decreased as the distance from tumor margin increased, regardless of the tumor cell presence, whereas GD3 correlated with neoplastic infiltration. In BAT, NG2 was coexpressed with a-smooth muscle actin (α-SMA) in pericytes and with nestin in the endothelium. Higher levels of NG2 mRNA and protein were found in GCSCs while GD3 synthase was expressed at similar levels in the 2 CSC populations. PCSCs had lower tumorigenicity than GCSCs. These data suggest the possible involvement of GD3 and NG2 in pre/pro-tumorigenic events occurring in the complex microenvironment of the tissue surrounding GBM.
AB - Characterization of tissue surrounding glioblastoma (GBM) is a focus for translational research because tumor recurrence invariably occurs in this area. We investigated the expression of the progenitor/ stem cell markers GD3 ganglioside and NG2 proteoglycan in GBM, peritumor tissue (brain adjacent to tumor, BAT) and cancer stem-like cells (CSCs) isolated from GBM (GCSCs) and BAT (PCSCs). GD3 and NG2 immunohistochemistry was performed in paired GBM and BAT specimens from 40 patients. Double-immunofluorescence was carried out to characterize NG2-positive cells of vessel walls. GD3 and NG2 expression was investigated in GCSCs and PCSCs whose tumorigenicity was also evaluated in Scid/bg mice. GD3 and NG2 expression was higher in tumor tissue than in BAT. NG2 decreased as the distance from tumor margin increased, regardless of the tumor cell presence, whereas GD3 correlated with neoplastic infiltration. In BAT, NG2 was coexpressed with a-smooth muscle actin (α-SMA) in pericytes and with nestin in the endothelium. Higher levels of NG2 mRNA and protein were found in GCSCs while GD3 synthase was expressed at similar levels in the 2 CSC populations. PCSCs had lower tumorigenicity than GCSCs. These data suggest the possible involvement of GD3 and NG2 in pre/pro-tumorigenic events occurring in the complex microenvironment of the tissue surrounding GBM.
KW - Brain adjacent to tumor
KW - Cancer stem cells
KW - GD3 ganglioside
KW - Glioblastoma
KW - NG2 proteoglycan
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U2 - 10.1093/jnen/nlv012
DO - 10.1093/jnen/nlv012
M3 - Article
C2 - 26792897
AN - SCOPUS:84960324161
SN - 0022-3069
VL - 75
SP - 134
EP - 147
JO - Journal of Neuropathology and Experimental Neurology
JF - Journal of Neuropathology and Experimental Neurology
IS - 2
ER -