PP01.57 Evaluation of the Metabolism of the Biogenic Amines on the Neuroendocrine Differentiation of A549 Adenocarcinoma Cells

One of the major causes of death by cancer is lung cancer, and the additional presence of neuroendocrine phenotype has been correlated to a worsened outcome in patients due to an increased number of peripheral tumor cells, drug-resistant tumors, and a higher percentage of metastasis. The process where one somatic cell type changes into another cell type without passing through the pluripotent state to generate functional cells is called transdifferentiation. This transdifferentiation has been described in vitro and in vivo for many cancer cell types; such as prostate, pancreas, liver and lung; in vitro, the induction has been observed by the exposure to different stimuli (i.e. cAMP analogs, IL-6, ionizing radiation, among others). The characteristics of the in vitro transdifferentiated cells with neuroendocrine phenotype are the low proliferation rate, dense chromatin, neurite-like projections, and the presence of secretory granules with neuroendocrine markers expression. Furthermore, the development of mature granules involves calcium influx, acidification, prohormone processing, and the uptake of amines (i.e. serotonin, 5-HT) through vesicular monoamine transporters. In particular, the significant increase of 5-HT and decrease of Dopamine (DA) in A549 neuroendocrine transdifferentiated (A549NED) cells was previously reported by our group suggesting the presence of mature secretory granules in transdifferentiated cells. For that matter, the purpose of this study was to determine the metabolites of the biogenic amines 5-HT (5HIIA) and DA (DOPAC and HVA) secreted by A549NED cells to understand the influence of this metabolism on the autocrine or paracrine signaling of the tumor microenvironment.