Functional Characterization of Purinergic Signaling in HOG Human Oligodendroglioma Cell Line: Tumor-Suppressive Role of the P2Y1 Receptor

Oligodendrogliomas are diffuse low-grade gliomas of the adult central nervous system characterized by high recurrence rates and limited therapeutic options. Extracellular nucleotide signaling via purinergic receptors (P2X and P2Y) regulates pathophysiological processes in various brain tumors; however, its specific role in oligodendrogliomas remains unexplored. Here, we characterized the purinergic receptor profile in HOG cells, a human oligodendroglioma cell line, and evaluated the specific impact of P2Y1 receptor activation on tumor cell dynamics. Single-cell calcium imaging experiments demonstrated that extracellular ATP increases intracellular calcium concentration through both extracellular influx and internal store mobilization. Expression analyses at transcript and protein levels identified ionotropic P2X4 and P2X5 receptors, alongside metabotropic P2Y1, P2Y2, and P2Y4 receptors. Furthermore, the calcium responses induced by selective P2Y agonists confirmed functional responses for P2Y1 and P2Y2/P2Y4 receptors. Finally, long-term time-lapse videomicroscopy combined with single-cell lineage tracking revealed that P2Y1 activation reduced cell proliferation, prolonged cell cycle duration, tended to reduce migratory velocity, and triggered cell death. Pre-incubation with the selective P2Y1 antagonist MRS2179 completely abrogated these effects. Taken together, our findings provide the first evidence of a functional purinergic network in HOG human oligodendroglioma cell line and highlight the P2Y1 receptor as a tumor-suppressive candidate and potential therapeutic target for oligodendroglioma management.