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

Author

Listed:
  • Bárbara Adem

    (Universidade do Porto
    Universidade do Porto)

  • Nuno Bastos

    (Universidade do Porto
    Universidade do Porto)

  • Carolina F. Ruivo

    (Universidade do Porto)

  • Sara Sousa-Alves

    (Universidade do Porto)

  • Carolina Dias

    (Universidade do Porto
    Universidade do Porto)

  • Patrícia F. Vieira

    (Universidade do Porto
    Universidade do Porto)

  • Inês A. Batista

    (Universidade do Porto
    Universidade do Porto)

  • Bruno Cavadas

    (Universidade do Porto)

  • Dieter Saur

    (Technical University Munich
    German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK))

  • José C. Machado

    (Universidade do Porto
    Universidade do Porto
    P.CCC Porto Comprehensive Cancer Center Raquel Seruca)

  • Dawen Cai

    (University of Michigan
    University of Michigan
    University of Michigan)

  • Sonia A. Melo

    (Universidade do Porto
    Universidade do Porto
    P.CCC Porto Comprehensive Cancer Center Raquel Seruca)

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.

Suggested Citation

  • Bárbara Adem & Nuno Bastos & Carolina F. Ruivo & Sara Sousa-Alves & Carolina Dias & Patrícia F. Vieira & Inês A. Batista & Bruno Cavadas & Dieter Saur & José C. Machado & Dawen Cai & Sonia A. Melo, 2024. "Exosomes define a local and systemic communication network in healthy pancreas and pancreatic ductal adenocarcinoma," Nature Communications, Nature, vol. 15(1), pages 1-22, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45753-7
    DOI: 10.1038/s41467-024-45753-7
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    References listed on IDEAS

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    1. Mathilde Mathieu & Nathalie Névo & Mabel Jouve & José Ignacio Valenzuela & Mathieu Maurin & Frederik J. Verweij & Roberta Palmulli & Danielle Lankar & Florent Dingli & Damarys Loew & Eric Rubinstein &, 2021. "Specificities of exosome versus small ectosome secretion revealed by live intracellular tracking of CD63 and CD9," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    2. Ayuko Hoshino & Bruno Costa-Silva & Tang-Long Shen & Goncalo Rodrigues & Ayako Hashimoto & Milica Tesic Mark & Henrik Molina & Shinji Kohsaka & Angela Di Giannatale & Sophia Ceder & Swarnima Singh & C, 2015. "Tumour exosome integrins determine organotropic metastasis," Nature, Nature, vol. 527(7578), pages 329-335, November.
    3. Yuqin Men & Julia Yelick & Shijie Jin & Yang Tian & Ming Sum R. Chiang & Haruki Higashimori & Eoin Brown & Rachel Jarvis & Yongjie Yang, 2019. "Exosome reporter mice reveal the involvement of exosomes in mediating neuron to astroglia communication in the CNS," Nature Communications, Nature, vol. 10(1), pages 1-18, December.
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