NON-NEURONAL CHOLINERGIC SYSTEM MODULATES THE CROSS-TALK BETWEEN THE IMMUNE SYSTEM AND GLIOBLASTOMA CELLS

FONTANA V; SABBIONE F; ALCAIN J; BLEJER J; SALAMONE G; MOVERER L; GORI MS; FERNÁNDEZ RJ; CANDOLFI M; ASAD AS; ERRA DÍAZ F; VERMEULEN M; GRASSI BASSINO A

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

SAI

Glioblastoma multiforme (GBM) is the deadliest and most commontype of human primary brain tumor. This tumor is defined by thehallmark features of uncontrolled cellular proliferation, diffuse infiltration,robust angiogenesis, resistance to apoptosis and genomicinstability. Acetylcholine is a neurotransmitter which can also modulatescell survival, proliferation and differentiation in neuronal andnon-neuronal cells such as immune cells, which has been referredto as a ?non-neuronal cholinergic system?. The aim of this work wasto elucidate the relevance of the non-neuronal cholinergic system inthe interaction between immune and GBM cells. We first evaluatedthe expression of acetylcholine receptors in human GBM cell linesby fluorescence microscopy. We found that both U251 and U373 humanGBM cells express acetylcholine muscarinic receptors M1 andM3. In order to evaluate whether the cholinergic system affects thecross-talk with immune cells, human U251 cells were co-culturedwith human dendritic cells (DC) in the presence of cholinergic agonists(carbachol and muscarine). Mononuclear cells were isolatedfrom buffy coats of healthy adult nonsmoker volunteer and CD14+cells were then isolated by positive selection and then were culturedwith GM-CSF and IL-4. The co-cultures were incubated in the presenceof carbachol 10-8 M) and muscarine (10-8M). We found thatU251 cells upregulated the expression of CD86 in DCs as assessedby flow cytometry in presence of carbachol and muscarine with respectto control co-cultures (p