Exosomes define a local and systemic communication network in healthy pancreas and in pancreatic ductal adenocarcinoma
Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease. Understanding its biology is crucial for finding effective therapies. Exosomes have been implicated in cancer, but their behavior in living systems remains poorly understood. We aimed to map the spatiotemporal distribution of exosomes from both healthy pancreas and PDAC to determine their biological significance. To achieve this, we developed a genetically engineered mouse model (ExoBow) to trace spontaneous exosomes communication. Within the PDAC microenvironment, cancer cells establish preferential communication routes with cancer associated fibroblasts and endothelial cells. The latter is a conserved event in the healthy pancreas. Inhibiting exosomes secretion in both scenarios significantly enhanced angiogenesis, underscoring the contribution of exosomes to the vascularization of the organ and to cancer. Inter-organ communication is significantly increased in PDAC, and the thymus is a sustained target in both contexts. PDAC cells also communicate with the kidneys and lungs, and the healthy pancreas with bone-marrow, brain, and intestines. In sum, we found that exosomes mediate an organized communication network in vivo that controls angiogenesis locally, both in the healthy pancreas and PDAC, and that targets the thymus also in both conditions, unravelling their potential role in central immune surveillance and anti-tumor immune response.