Exosomes define a local and systemic communication network in healthy pancreas and pancreatic ductal adenocarcinoma

• Type: Article in International Scientific Journal
• Date: 2024

Authors

Adem, B (Author) Other; Bastos, N (Author) Other; Ruivo, CF (Author) Other; Sousa-Alves, S (Author) Other; Dias, C (Author) Other; Vieira, PF (Author) Other; Batista, IA (Author) Other; Cavadas, B (Author) Other; Saur, D (Author) Other; Machado JC (Author) FMUP; Cai, DW (Author) Other; Melo, SA (Author) FMUP

Journal

Title: Nature Communications

Vol. 362

ISSN: 2041-1723

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 0 Citations

Scopus - 0 Citations

Other information

Authenticus ID: P-010-0WS

DOI: 10.1038/s41467-024-45753-7

Abstract (EN): 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. The behavior of exosomes in vivo is not completely elucidated. Here the authors develop a genetically engineered mouse model (ExoBow) to trace the distribution of exosomes, showing local and inter-organ communication networks, either specific or shared between healthy pancreas and pancreatic ductal adenocarcinoma.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 22