Glioma stem-like cells (GSCs) are a subpopulation of neoplastic cells with characteristics of stem cells which have
been described on human glioblastoma. They play a pivotal role in tumour angiogenesis, malignancy and invasion process. They use the
vascular extracellular matrix to infiltrate. In this work we relate the appearance of GSCs and the angiogenesis process during the development
of a rat endogenous experimental glioma model.
Glioblastomas were induced in Sprague Dawley rats by transplacentary administration of Ethylnitrosourea (ENU). Identification
of ENU-Glioma stages (early, intermediated and advanced) was performed by MNR T2 and T1-images and histopathology
diagnosis. Microvascular network adaptation and angiogenesis process during the tumour progression was showed by LEA histochemistry
and doble-immunofluorescence of GluT-1(glucose transporter-1), EBA (endothelial barrier specific antigen), and vascular endothelial growth
factor (VEGF)165. The identification of GSC was performed by glioma stem cell marker (CD133/Prominin-1), neural stem cells (Nestin) and
anti-GFAP antibodies.
Nestin+ cells were found in every stage of tumour development, whereas CD133 + cells were only present since intermediates
stages corresponding with VEGF165 overexpression and “angiogenic switch”. Some of the GSCs coexpressing Nestin-CD133-VEGF165
were showed in three distributions patterns: 1- isolated in the tumour periphery areas; 2- intratumor niches of numerous small cells and 3-
niches of cells around the tortuous and aberrant vessel (intermediate-advanced stages). Only peripheral cells are stained for GFAP. Nestin+
cells predominate over the CD133+ in intratumor niches but not around vessels.
GSCs are distributed in these experimental gliomas as well as in human glioblastoma, shaping niches into perivascular
or intratumoral hypoxic areas. Following CD133 expression, our findings corroborate the hypothesis that GSCs have a close relationship
with angiogenic switch, and neoplastic microvascular network.
This work was presented at the IBRO‘s 2011 World Congress of Neuroscience. Florence. July 14-19
