title: Oligodendroglioma cells shed microvesicles which contain TRAIL as well as molecular chaperones and induce cell death in astrocytes.
abstract: Microvesicles (MVs) shed from G26/24 oligodendroglioma cells were previously reported to cause a reproducible, dose-dependent, inhibitory effect on neurite outgrowth, and eventually neuronal apoptosis, when added to primary cultures of rat cortical neurons. These effects were reduced but not abolished by functional monoclonal antibodies against Fas-L. In order to investigate whether MVs contain other factors able to induce cell death, we tested them for TRAIL and found clear evidence of its presence in the vesicles. This finding suggests the possibility that Fas-L and TRAIL cooperate in inducing brain cell death. Aimed at understanding the route through which the vesicles deliver their messages to the target cells, we labeled oligodendroglioma cells with radioactive methionine and then added the labeled vesicles shed from tumor cells to unlabeled astrocytes in culture. Here we report that labeled proteins were delivered to the test cells. In order to investigate whether astrocytes, like neurons, are sensitive to oligodendroglioma-derived vesicles, MVs were prepared from media conditioned by G26/24 oligodendroglioma cells and added to primary cultures of rat cortical astrocytes. These cells were clearly more resistant than neurons to microvesicle-induced damage: a high dose (40 µg) of shed MVs induced cell death in only about 40% of astrocytes. Finally, we demonstrated that Hsp70 is specifically enriched in MVs which also contain, even if at lower level, the Hsc70 constitutive chaperone.
authors.affiliation: Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche, Università degli Studi di Palermo, Palermo, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Lo Cicero
authors.forename: Gabriella
authors.initials: G
authors.lastname: Schiera
authors.forename: Patrizia
authors.initials: P
authors.lastname: Proia
authors.forename: Patrizia
authors.initials: P
authors.lastname: Saladino
authors.forename: Giovanni
authors.initials: G
authors.lastname: Savettieri
authors.forename: Carlo Maria
authors.initials: CM
authors.lastname: Di Liegro
authors.forename: Italia
authors.initials: I
authors.lastname: Di Liegro
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002450:Cell Communication; D016923:Cell Death / Q000187:drug effects; D055252:Cell-Derived Microparticles / Q000737:chemistry* / Q000378:metabolism*; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000737:chemistry / Q000494:pharmacology; D050883:HSC70 Heat-Shock Proteins / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism*; D009837:Oligodendroglioma / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*
chemical_list: D017077:Culture Media, Conditioned; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D018832:Molecular Chaperones; D053221:TNF-Related Apoptosis-Inducing Ligand