G26/24 extracellular microvesicles contain both H1° protein and RNA

Abstract

Extracellular vesicles (EVs) are released into the extracellular space from both tumor and normal brain cells. By releasing EVs which contain FGF2 and VEGF1-2, astrocytes and neurons, co-cultured with brain capillary endothelial cells, are for example able to induce them to form a blood-brain barrier-like monolayer. On the other hand, membrane microvesicles (MVs) shed from G26/24 oligodendro­glioma cells, when added to primary cultures of rat cortical neurons, induce neuronal damage; the damaging effects include a strong reduction of neurite outgrowth, and apoptosis in about 75% of the cells3. The same amount of shed MVs induce apoptosis in about 40% of astrocytes4. These effects are probably due to Fas Ligand and TRAIL, two proteins, present in G26/24 vesicles, with well-known cell death inducing ability5-6. EV-mediated horizontal transfer of labeled proteins from oligodendroglioma cells to astrocytes in culture was also noticed4. We found that, in cultured astrocytes, as previously found in developing rat brain, the amount of the H1° linker histone increases during differentiation, while the level of its mRNA decreases, suggesting that its expression is mainly regulated at the post-transcriptional level7. On the other hand, G26/24 maintain high levels of both H1° protein and mRNA. We recently found that these tumor cells release both H1° protein and mRNA, through EVs, into the culture medium8. We suggest that G26/24 oligodendroglioma cells, and possibly other tumor cells, can escape differentiation cues, and continue to proliferate by eliminating proteins, such as the H1° linker histone (and its mRNA) into the extracellular space. Schiera G et al. J Cell Mol Med 2007, 138-94. Proia P et al. Int J Mol Med 2008, 21: 63-7. D’Agostino S et al. Int J Oncol 2006, 29:1075-85. Lo Cicero A et al. Int J Oncol 2011, 39: 1353-57. Albanese J et al. Blood 1998, 91: 3862-74. Abrahams VM et al. Cancer Res 2003, 63: 5573-81. Castiglia D et al. Neurochem Res 1994, 19:1531-37. Schiera G et al. Int J Oncol. 2013, 43:1771-76.