Endothelial trans-differentiation in glioblastoma recurring after radiotherapy

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

Risultato della ricerca: Contributo in rivistaArticolo in rivista

13 Citazioni (Scopus)

Abstract

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.
Lingua originaleEnglish
pagine (da-a)1361-1366
Numero di pagine6
RivistaModern Pathology
Volume31
DOI
Stato di pubblicazionePubblicato - 2018

Keywords

  • Glioblastoma
  • angiogenesis

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