TY - JOUR
T1 - Angiogenesis in human brain tumors
T2 - Screening of drug response through a patient-specific cell platform for personalized therapy
AU - Guarnaccia, Laura
AU - Navone, Stefania Elena
AU - Trombetta, Elena
AU - Cordiglieri, Chiara
AU - Cherubini, Alessandro
AU - Crisà, Francesco Maria
AU - Rampini, Paolo
AU - Miozzo, Monica
AU - Fontana, Laura
AU - Caroli, Manuela
AU - Locatelli, Marco
AU - Riboni, Laura
AU - Campanella, Rolando
AU - Marfia, Giovanni
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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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U2 - 10.1038/s41598-018-27116-7
DO - 10.1038/s41598-018-27116-7
M3 - Article
AN - SCOPUS:85048339143
VL - 8
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 5748
ER -