The overall goal of this joint research proposal is to characterize the effect of macrophage-derived exosomes (MDEs) on cancer cell progression. We hypothesized that tumor associated macrophages transmit specific miRNAs via exosomes to cancer cells, promoting tumor growth by reprogramming glucose metabolism. Based on our preliminary data that was presented above, we will further explore the role of exosomes as a vehicle to selectively modulate metabolic pathways in PDA tumor.  The aims of the current study focus on three elements of the stroma-neoplastic circuit: 1) Exosomal signaling between macrophages and cancer cells, 2) The influence of specific exosomal-derived miRNA on cancer cell physiology and 3) the effect of MDEs and their content on cancer cells’ glucose metabolism.