Gliomas are the most common brain tumours with a poor prognosis due to their aggressiveness and propensity for recurrence. The 18 kDa mitochondrial translocator protein (TSPO) has been suggested as a promising diagnostic and therapeutic target in gliomas. The rationale behind this potential application is based on two main features. Firstly, it has been postulated that TSPO represents a component of the mitochondrial permeability transition (MPT) pore, that plays a key role in the control of cell death pathways. Indeed, several TSPO ligands, modulating the opening of the MPT-pore, show anti-proliferative and pro-apoptotic activities in various tumoural cells. Secondly, TSPO expression has been found to be increased in several tumors and cancer cell lines relative to untransformed cells. A positive correlation between TSPO expression levels and tumorigenicity of cancer cells, including gliomas, has been also documented leading to the hypothesis that the presence of TSPO may be a determinant factor for the aggressive phenotypes. However, up to now direct evidences on the relation between TSPO expression levels and metastatic potential of glioma cells as well as the relation between TSPO density and cell susceptibility to TSPO ligands are limited. Here, we evaluated the pro-apototic activity of specific TSPO ligands and extimated the influence of TSPO density on glioma cell aggressiviness.
Cell survival/death processes: Role of the mitochondrial Tranlocator Protein (TSPO) ligands
DA POZZO, ELEONORA;ROSSI, LEONARDO;SIMORINI, FRANCESCA;SALVETTI, ALESSANDRA;TALIANI, SABRINA;DA SETTIMO PASSETTI, FEDERICO;MARTINI, CLAUDIA
2009-01-01
Abstract
Gliomas are the most common brain tumours with a poor prognosis due to their aggressiveness and propensity for recurrence. The 18 kDa mitochondrial translocator protein (TSPO) has been suggested as a promising diagnostic and therapeutic target in gliomas. The rationale behind this potential application is based on two main features. Firstly, it has been postulated that TSPO represents a component of the mitochondrial permeability transition (MPT) pore, that plays a key role in the control of cell death pathways. Indeed, several TSPO ligands, modulating the opening of the MPT-pore, show anti-proliferative and pro-apoptotic activities in various tumoural cells. Secondly, TSPO expression has been found to be increased in several tumors and cancer cell lines relative to untransformed cells. A positive correlation between TSPO expression levels and tumorigenicity of cancer cells, including gliomas, has been also documented leading to the hypothesis that the presence of TSPO may be a determinant factor for the aggressive phenotypes. However, up to now direct evidences on the relation between TSPO expression levels and metastatic potential of glioma cells as well as the relation between TSPO density and cell susceptibility to TSPO ligands are limited. Here, we evaluated the pro-apototic activity of specific TSPO ligands and extimated the influence of TSPO density on glioma cell aggressiviness.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
