Journal Article

Endothelial trans-differentiation in glioblastoma recurring after radiotherapy

De Pascalis, Ivana, Pallini, Roberto, Pacioni, Simone, Giannetti, Stefano, Larocca, Luigi M., Dejana, Elisabetta, Malinverno, Matteo, D’Alessandris, Quintino Giorgio, Ricci-Vitiani, Lucia, Morgante, Liliana, Martini, Maurizio

2018

Overview

We hypothesized that in glioblastoma recurring after radiotherapy, a condition whereby the brain endothelium undergoes radiation-induced senescence, tumor cells with endothelial phenotype may be relevant for tumor neovascularization. Matched glioblastoma samples obtained at primary surgery and at surgery for tumor recurrence after radiotherapy, all expressing epidermal growth factor receptor variant III (EGFRvIII), were assessed by a technique that combines fluorescent in situ hybridization (FISH) for the EGFR/CEP7 chromosomal probe with immunostaining for endothelial cells (CD31) and activated pericytes (α Smooth Muscle Actin). Five EGFRvIII-expressing paired primary/recurrent glioblastoma samples, in which the tumor cells showed EGFR/CEP7 amplification, were then assessed by CD31 and α Smooth Muscle Actin immunofluorescence. In glomeruloid bodies, the ratio between CD31+ cells with amplified EGFR/CEP7 signal and the total CD31+ cells was 0.23 ± 0.09 (mean ± sem) and 0.63 ± 0.07 in primary tumors and in recurrent ones, respectively ( p  < 0.002, Student- t test). In capillaries, the ratio of CD31+ cells with amplified EGFR/CEP7 over the total CD31+ cells lining the capillary lumen was 0.21 ± 0.06 (mean ± sem) and 0.42 ± 0.07 at primary surgery and at recurrence, respectively ( p  < 0.005, Student- t test). Expression of α Smooth Muscle Actin by cells with EGFR/CEP7 amplification was not observed. Then, in glioblastoma recurring after radiotherapy, where the brain endothelium suffers from radiation-induced cell senescence, tumor-derived endothelium plays a role in neo-vascularization.

• Publisher: Nature Publishing Group US,Elsevier Limited
• Subject: 13/1 / 13/106 / 13/51 / 14/32 / 631/136/16/1646 / 631/80/509 / 64/60 / 692/53/2421 / 692/699/67/1922 / Actin / Animals / Brain cancer / Brain Neoplasms - genetics / Brain Neoplasms - pathology / Brain Neoplasms - radiotherapy / Capillaries / Cell Transdifferentiation - physiology / Endothelial cells / Endothelial Cells - metabolism / Endothelial Cells - pathology / Endothelial Cells - radiation effects / Endothelium / Epidermal growth factor / Epidermal growth factor receptors / ErbB Receptors - genetics / ErbB Receptors - metabolism / Fluorescence in situ hybridization / Glioblastoma / Glioblastoma - genetics / Glioblastoma - pathology / Glioblastoma - radiotherapy / Human Umbilical Vein Endothelial Cells - metabolism / Human Umbilical Vein Endothelial Cells - pathology / Human Umbilical Vein Endothelial Cells - radiation effects / Humans / Immunofluorescence / In Situ Hybridization, Fluorescence / Laboratory Medicine / Medicine / Medicine & Public Health / Mice / Neoplasm Recurrence, Local - genetics / Neoplasm Recurrence, Local - pathology / Pathology / Pericytes / Phenotypes / Radiation therapy / Senescence / Smooth muscle / Surgery / Tumor cells / Tumors / Vascularization