Fig. 8. Schematic of the intra- and inter- pancreas communication established by CD63 positive exosomes in PDAC.

The ExoBow mouse model can be crossed with specific Flp and Cre lines driven by the Pdx1-pancreas promoter which will render the conditional expression of CD63-XFP reporter proteins by pancreas cells. Crossing this model with well-stablished PDAC genetically engineered mouse models, enables the assessment of CD63 exosomes biodistribution locally and systemically in both healthy and PDAC contexts. Our work demonstrates an intra-pancreas connectome mediated by pancreas-derived exosomes mainly with CAFs (in a PDAC-specific context), followed by endothelial cells and, in lower amounts, with cells of the immune system. We were also able to demonstrate that the inter-pancreas connectome mediated by pancreas-derived exosomes varies from physiological conditions to a cancer context. Furthermore, we show that these routes of communication also vary along PDAC progression. PDAC, pancreatic ductal adenocarcinoma; CAFs, cancer-associated fibroblasts. Schemes created with BioRender.com.