The communication network of pancreatic cancer

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The communication network of pancreatic cancer

Friday, 31.05.2024
Recent advancements in mouse models for studying exosomes have provided new insights into their roles in various biological contexts. Exosomes are tiny particles that cells release to communicate with each other. Using a new genetic mouse model, we tracked exosomes from pancreas cells and studied their behavior during pancreatic ductal adenocarcinoma, a type of pancreatic cancer.
 
Our findings show that cell communication is coordinated, not random. In a healthy pancreas, exosomes help prevent the growth of new blood vessels, maintaining organ health. In pancreatic cancer, however, exosomes promote blood vessel growth, aiding cancer progression. We also found that exosomes interact with cancer-associated fibroblasts, influencing the tumor environment and potentially affecting cancer outcomes.
 
Exosomes from pancreatic cancer were found to communicate more with other organs compared to those from a healthy pancreas, especially accumulating in the kidneys and thymus. Interestingly, while exosomes also reached the lungs in cancer, they were less prevalent in the liver, despite it being a common site for cancer spread.
 
By analyzing the content of these exosomes, we revealed how they impact surrounding cells and contribute to the tumor environment. This study shows that both the quantity and diversity of exosomes in pancreatic cancer significantly influence the tumor's microenvironment.
 
In summary, our research provides a deeper understanding of how exosomes affect the pancreatic environment in health and disease, offering potential improvements in cancer patient care and advancing exosomes research.
 

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

 

Linkhttps://www.nature.com/articles/s41467-024-45753-7?utm_campaign=related_content&utm_source=HEALTH&utm_medium=communities#Ack1