NO NEURONAL CHOLINERGIC SYSTEM INFLUENCE IN THE PROGRESSION OF U251MG HUMAN GLIOBLASTOMA CELL LINE AND ITS IMPACT ON THE IMMUNE RESPONSE

MOVERER L; GORI MS; MORENO AYALA, MARIELA A.; ASAD A; ALCAIN J; SCORDO W; VERMEULEN M; CANDOLFI, MARIANELA; SALAMONE G

Mar del Plata

Congreso; Reunión Conjunta SAIC-SAI-SAFE 2016; 2016

)lioblastoma multiforme )$/ is the deadliest and most common type of human primary brain tumor. This tumor is defined by the hallmarM features of uncontrolled cellular proliferation, diffuse infiltration, propensity for necrosis, robust angiogenesis, intense resistance to apoptosis and genomic instability. Acetylcholine ACh is a neurotransmitter Yhich can also modulates cell survival, proliferation and differentiation in neuronal and nonneuronal cells such as immune cells, Yhich has been referred to as a őnonneuronal cholinergic system?. The aim of this YorM is to elucidate the relevance of the nonneuronal cholinergic system in the interaction immune)$/ cells. /ethods Human 7 )$/ cells Yere cocultured Yith human dendritic cells &C obtained from healthy adult volunteer. /ononuclear cells Yere isolated from buffy coats of healthy adult nonsmoMer volunteer and C& cells Yere then isolated by positive selection and then Yere cultured Yith )/CSF and +L. The cells Yere cultered in the presence of cholinergic agonists (carbachol, muscarine and nicotine) and antagonists (atropine and mecamelamine) and evaluated DC maturation. Results: We found that coculture of dendritic cells Yith 7 cells in the presence of carbachol and nicotine treatment increased the release of +L 2, as Yell as the expression of C& and HLA&4, Ye did not find difference in the production of +L citoMine. These effects Yere completely blocMed Yhen the coculture Yas treated Yith selective antagonists for mACh4 and nACh4, Atropine and /ecamelamina receptors respectively. Conclusions The cholinergic system stimulates the cytoMines production in 7 and &C cells and modulates the activation and maturation of &C. 1ur findings suggest that the no neuronal cholinergic system could emerge as a therapeutic target for the immunotherapy of )$/.