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Angiogenesis in human brain tumors: screening of drug response through a
patient-specific cell platform for personalized therapy
#MMPMID29884885
Guarnaccia L
; Navone SE
; Trombetta E
; Cordiglieri C
; Cherubini A
; Crisà FM
; Rampini P
; Miozzo M
; Fontana L
; Caroli M
; Locatelli M
; Riboni L
; Campanella R
; Marfia G
Sci Rep
2018[Jun]; 8
(1
): 8748
PMID29884885
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Gliomas are the most common brain tumors, with diverse biological behaviour.
Glioblastoma (GBM), the most aggressive and with the worst prognosis, is
characterized by an intense and aberrant angiogenesis, which distinguishes it
from low-grade gliomas (LGGs) and benign expansive lesions, as meningiomas
(MNGs). With increasing evidence for the importance of vascularization in tumor
biology, we focused on the isolation and characterization of endothelial cells
(ECs) from primary GBMs, LGGs and MNGs. Gene expression analysis by Real-Time
PCR, immunofluorescence and flow cytometry analysis, tube-like structures
formation and vascular permeability assays were performed. Our results showed a
higher efficiency of ECs to form a complex vascular architecture, as well as a
greater impairment of a brain blood barrier model, and an overexpression of
pro-angiogenic mediators in GBM than in LGG and MNG. Furthermore, administration
of temozolomide, bevacizumab, and sunitinib triggered a different proliferative,
apoptotic and angiogenic response, in a dose and time-dependent manner. An
increased resistance to temozolomide was observed in T98G cells co-cultured in
GBM-EC conditioned media. Therefore, we developed a novel platform to reproduce
tumor vascularization as "disease in a dish", which allows us to perform
screening of sensitivity/resistance to drugs, in order to optimize targeted
approaches to GBM therapy.
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