Unraveling the role of extracellular vesicles in mediating the crosstalk between mast cells and cancer cells in the tumor microenvironment

Mast cells (MC) are cells of the immune system that are best known for their role in allergy. They respond to a variety of stimuli by releasing inflammatory mediators, part of which are prestored in secretory granules. The repertoire of mediators released by MCs depends on their stimulus type. Recent studies in our laboratory have documented MC activation, leading to gene upregulation, upon contact with cancer cells or cancer cell derived extracellular vesicles (EVs), by a mechanism involving autocrine formation of adenosine and signaling by the A3 adenosine receptor. Here we show that following their activation by membranes derived from H1299 non small cell lung carcinoma cells (NSCLC), conditions that recapitulate contact mediated activation, MCs release exosomes, whose microRNA (miR) content is modified. We explored the signaling pathways that define the exosomal miR content and show that unlike gene upregulation that occurs in MCs following their activation by contact with NSCLC cells, miR upregulation and release by exosomes are independent of adenosinergic signalling. These results demonstrate the existence and functional diversity of signalling pathways that are elicited in NSCLC-activated MCs.