THE NON-NEURONAL CHOLINERGIC SYSTEM IN THE GLIOBLASTOMA CELLS

MONTES M; GORI MS; VERMEULEN M; ITURRIZAGA MEZA JK; ASAD AS; BELLI C; SALAMONE G; FONTANA VA; BESTACH Y; CANDOLFI M

Mar del Plata

Congreso; Reunión conjunta SAIC-SAI-SAFIS 2018; 2018

Glioblastoma multiforme (GBM) is the deadliest and most common type of human primary brain tumor. This tumor is defined by the hallmark features of uncontrolled cellular proliferation, diffuse infiltration, robust angiogenesis and resistance to apoptosis. Acetylcholine is a neurotransmitter which can also modulate cell survival, proliferation and differentiation in neuronal and non-neuronal cells such as immune cells and tumors cells, among others, which has been referred to as a ?non-neuronal cholinergic system?. The aim of this work was to elucidate the relevance of the non-neuronal cholinergic system in GBM cells and the relevance of the dendritic cells (DC). First, we observed the expression of acetylcholine receptors in human GBM cell lines by fluorescence microscopy and found that both U251 and U373 human GBM cells express acetylcholine muscarinic receptors M1 and M3. The expression of the M3 was also observed by immunohistochemestry in experimental GL26 tumors growing in the brain of immunocompetent mice.We analyzed whether the cholinergic system modulates the apoptotic response of human GBM U373 cells. Apoptosis was assessed by flow cytometry by annexin propidium iodidestaining. We observed a clear increased of the apoptosic rate when U373 cells were incubated with carbachol (10-9M) (p