Associação Portuguesa de Investigação em Cancro
The communication network of pancreatic cancer
The communication network of pancreatic cancer

Authors and Affiliations:
Bárbara Adem1,2, Nuno Bastos1,2, Carolina F. Ruivo1, Sara Sousa-Alves1, Carolina Dias1,3, Patrícia F. Vieira1,3, Inês A. Batista1,2, Bruno Cavadas1, Dieter Saur4,5, José C. Machado1,6,7, Dawen Cai8-10, Sonia A. Melo1,6,7
1i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal.
2Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, Portugal.
3Faculdade de Medicina, Universidade do Porto, Portugal.
4Medical Clinic and Polyclinic II, Klinikum rechts der Isar, Technical University Munich, Germany.
5German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany.
6Departamento de Patologia, Faculdade de Medicina, Universidade do Porto, Portugal.
7P.CCC Porto Comprehensive Cancer Center Raquel Seruca, Portugal.
8Department of Cell and Developmental Biology, Medical School, University of Michigan, Ann Arbor, Michigan, USA.
9Biophysics, LS&A, University of Michigan, Ann Arbor, Michigan, USA.
10Michigan Neuroscience Institute, University of Michigan, Ann Arbor, Michigan, USA.
Abstract:
Pancreatic ductal adenocarcinoma (PDAC), a lethal disease, requires a grasp of its biology for effective therapies. Exosomes, implicated in cancer, are poorly understood in living systems. Here we use the genetically engineered mouse model (ExoBow) to map the spatiotemporal distribution of exosomes from healthy and PDAC pancreas in vivo to determine their biological significance. We show that, within the PDAC microenvironment, cancer cells establish preferential communication routes through exosomes with cancer associated fibroblasts and endothelial cells. The latter being a conserved event in the healthy pancreas. Inhibiting exosomes secretion in both scenarios enhances angiogenesis, underscoring their contribution to vascularization and to cancer. Inter-organ communication is significantly increased in PDAC with specific organs as most frequent targets of exosomes communication occurring in health with the thymus, bone-marrow, brain, and intestines, and in PDAC with the kidneys, lungs and thymus. In sum, we find that exosomes mediate an organized intra- and inter- pancreas communication network with modulatory effects in vivo.
Journal: Nature Communications