Exosomes define a local and systemic communication network in healthy pancreas and pancreatic ductal adenocarcinoma
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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-45753-7 |
| _version_ | 1797274121454747648 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Bárbara Adem |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-07T14:53:50Z |
| format | Article |
| id | doaj.art-bc7d9ee1ccd04333abccf2b19c10a836 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-07T14:53:50Z |
| publishDate | 2024-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-bc7d9ee1ccd04333abccf2b19c10a8362024-03-05T19:33:16ZengNature PortfolioNature Communications2041-17232024-02-0115112210.1038/s41467-024-45753-7Exosomes define a local and systemic communication network in healthy pancreas and pancreatic ductal adenocarcinomaBárbara Adem0Nuno Bastos1Carolina F. Ruivo2Sara Sousa-Alves3Carolina Dias4Patrícia F. Vieira5Inês A. Batista6Bruno Cavadas7Dieter Saur8José C. Machado9Dawen Cai10Sonia A. Melo11i3S—Instituto de Investigação e Inovação em Saúde, Universidade do Portoi3S—Instituto de Investigação e Inovação em Saúde, Universidade do Portoi3S—Instituto de Investigação e Inovação em Saúde, Universidade do Portoi3S—Instituto de Investigação e Inovação em Saúde, Universidade do Portoi3S—Instituto de Investigação e Inovação em Saúde, Universidade do Portoi3S—Instituto de Investigação e Inovação em Saúde, Universidade do Portoi3S—Instituto de Investigação e Inovação em Saúde, Universidade do Portoi3S—Instituto de Investigação e Inovação em Saúde, Universidade do PortoMedical Clinic and Polyclinic II, Klinikum rechts der Isar, Technical University Munichi3S—Instituto de Investigação e Inovação em Saúde, Universidade do PortoDepartment of Cell and Developmental Biology, Medical School, University of Michigani3S—Instituto de Investigação e Inovação em Saúde, Universidade do PortoAbstract 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.https://doi.org/10.1038/s41467-024-45753-7 |
| spellingShingle | 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 Exosomes define a local and systemic communication network in healthy pancreas and pancreatic ductal adenocarcinoma Nature Communications |
| title | Exosomes define a local and systemic communication network in healthy pancreas and pancreatic ductal adenocarcinoma |
| title_full | Exosomes define a local and systemic communication network in healthy pancreas and pancreatic ductal adenocarcinoma |
| title_fullStr | Exosomes define a local and systemic communication network in healthy pancreas and pancreatic ductal adenocarcinoma |
| title_full_unstemmed | Exosomes define a local and systemic communication network in healthy pancreas and pancreatic ductal adenocarcinoma |
| title_short | Exosomes define a local and systemic communication network in healthy pancreas and pancreatic ductal adenocarcinoma |
| title_sort | exosomes define a local and systemic communication network in healthy pancreas and pancreatic ductal adenocarcinoma |
| url | https://doi.org/10.1038/s41467-024-45753-7 |
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