TSPO over-expression increases motility, transmigration and proliferation properties of C6 rat glioma cells.
Gliomas are one of the most malignant cancers. The molecular bases regulating the onset of such tumors are still poorly understood. The translocator protein (TSPO), formerly known as the peripheral-type benzodiazepine receptor, is a mitochondrial permeability transition (MPT)-pore protein robustly expressed in gliomas and involved in the regulation of apoptosis and cell proliferation. TSPO expression levels have been correlated with tumor malignancy. Here we describe the production of C6 rat glioma cells engineered to over-express the TSPO protein with the aim of providing the first direct evidence of a correlation between TSPO expression level and glioma cell aggressiveness. We observed that TSPO potentiates proliferation, motility and transmigration capabilities as well as the ability to overcome contact-induced cell growth inhibition of glioma cells. On the whole, these data demonstrate that TSPO density influences metastatic potential of glioma cells. Since several data suggest that TSPO ligands may act as chemotherapeutic agents, in this paper we also demonstrate that TSPO ligand-induced cell death is dependent on TSPO density. These findings suggest that the use of TSPO ligands as chemotherapeutic agents could be effective on aggressive tumor cells with a high TSPO expression level.
Rechichi
Mariarosa
M
Dipartimento di Morfologia Umana e Biologia Applicata, University of Pisa, Via Volta 4, Pisa, Italy.
Salvetti
Alessandra
A
Chelli
Beatrice
B
Costa
Barbara
B
Da Pozzo
Eleonora
E
Spinetti
Francesca
F
Lena
Annalisa
A
Evangelista
Monica
M
Rainaldi
Giuseppe
G
Martini
Claudia
C
Gremigni
Vittorio
V
Rossi
Leonardo
L
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D007546:Isoquinolines / Q000494:pharmacology; D008024:Ligands; D009361:Neoplasm Invasiveness; D051381:Rats; D011963:Receptors, GABA-A / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D014162:Transfection; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D000970:Antineoplastic Agents; D002352:Carrier Proteins; D007546:Isoquinolines; D008024:Ligands; D011963:Receptors, GABA-A; C069997:Tspo protein, rat; C037850:PK 11195