Angiogenesis in human brain tumors: Screening of drug response through a patient-specific cell platform for personalized therapy

Laura Guarnaccia, Stefania Elena Navone, Elena Trombetta, Chiara Cordiglieri, Alessandro Cherubini, Francesco Maria Crisà, Paolo Rampini, Monica Miozzo, Laura Fontana, Manuela Caroli, Marco Locatelli, Laura Riboni, Rolando Campanella, Giovanni Marfia

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number5748
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - Dec 1 2018

ASJC Scopus subject areas

  • General

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