Dysregulation of intercellular communication in vitro and in vivo via extracellular vesicles secreted by pancreatic duct adenocarcinoma cells and generated under the influence of the AG9 elastin peptide-conditioned microenvironment.

Autor: Nannan L; Université de Reims Champagne-Ardenne Laboratoire de Biochimie Médicale et Biologie Moléculaire, UFR Médecine Reims France.; CNRS UMR 7369 Matrice Extracellulaire et Dynamique Cellulaire Reims France.; KU Leuven, Department of Imaging and Pathology Biomedical MRI Leuven Belgium., Decombis S; Université de Reims Champagne-Ardenne Laboratoire de Biochimie Médicale et Biologie Moléculaire, UFR Médecine Reims France.; CNRS UMR 7369 Matrice Extracellulaire et Dynamique Cellulaire Reims France., Terryn C; PICT Platform University of Reims Champagne-Ardenne Reims France., Audonnet S; URCACyt Platform University of Reims Champagne-Ardenne Reims France., Michel J; Inserm, Université de Reims Champagne-Ardenne, P3Cell UMR-S1250, SFR CAP-SANTE Reims France., Brassart-Pasco S; Université de Reims Champagne-Ardenne Laboratoire de Biochimie Médicale et Biologie Moléculaire, UFR Médecine Reims France.; CNRS UMR 7369 Matrice Extracellulaire et Dynamique Cellulaire Reims France., Gsell W; KU Leuven, Department of Imaging and Pathology Biomedical MRI Leuven Belgium., Himmelreich U; KU Leuven, Department of Imaging and Pathology Biomedical MRI Leuven Belgium., Brassart B; Université de Reims Champagne-Ardenne Laboratoire de Biochimie Médicale et Biologie Moléculaire, UFR Médecine Reims France.; CNRS UMR 7369 Matrice Extracellulaire et Dynamique Cellulaire Reims France.
Jazyk: angličtina
Zdroj: Journal of extracellular biology [J Extracell Biol] 2024 Mar 07; Vol. 3 (3), pp. e145. Date of Electronic Publication: 2024 Mar 07 (Print Publication: 2024).
DOI: 10.1002/jex2.145
Abstrakt: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with poor prognosis due to its highly metastatic profile. Intercellular communication between cancer and stromal cells via extracellular vesicles (EVs) is crucial for the premetastatic microenvironment preparation leading to tumour metastasis. This study shows that under the influence of bioactive peptides derived from the extracellular matrix microenvironment, illustrated here by the AG-9 elastin-derived peptide (EDP), PDAC cells secrete more tumour-derived EVs. Compared to PDAC-derived EVs, tumour-derived EVs resulting from AG-9 treatment (PDAC AG-9-derived EVs) significantly stimulated cell proliferation. At constant amount, tumour-derived EVs were similarly taken up by PDAC and HMEC-1 cells. Tumour-derived EVs stimulated cell proliferation, migration, proteinase secretion, and angiogenesis. Bioluminescence imaging allowed tumour-derived EV/FLuc+ tracking in vivo in a PDAC mouse model. The biodistribution of PDAC AG-9-derived EVs was different to PDAC-derived EVs. Our results demonstrate that the microenvironment, through EDP release, may not only influence the genesis of EVs but may also affect tumour progression (tumour growth and angiogenesis), and metastatic homing by modifying the in vivo biodistribution of tumour-derived EVs. They are potential candidates for targeted drug delivery and modulation of tumour progression, and they constitute a new generation of therapeutic tools, merging oncology and genic therapy.
Competing Interests: None of the authors have any conflict to declare.
(© 2024 The Authors. Journal of Extracellular Biology published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.)
Databáze: MEDLINE
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