Matrix stiffness regulates the protein profile of extracellular vesicles of pancreatic cancer cell lines
The fibrotic stroma characterizing pancreatic ductal adenocarcinoma (PDAC) derives from a progressive tissue rigidification, which induces epithelial mesenchymal transition and metastatic dissemination. The aim of this study was to investigate the influence of matrix stiffness on PDAC progression by analyzing the proteome of PDAC-derived extracellular vesicles (EVs). PDAC cell lines (mPDAC and KPC) were grown on synthetic supports with a stiffness close to non-tumor (NT) or tumor tissue (T), and the protein expression levels in cell-derived EVs were analyzed by a quantitative MS<sup>E</sup> label-free mass spectrometry approach. Our analysis figured out 15 differentially expressed proteins (DEPs) in mPDAC-EVs and 20 DEPs in KPC-EVs in response to matrix rigidification. Up-regulated proteins participate to the processes of metabolism, matrix remodeling, and immune response, altogether hallmarks of PDAC progression. A multimodal network analysis revealed that the majority of DEPs are strongly related to pancreatic cancer. Interestingly, among DEPs, 11 related genes (ACTB/ANXA7/C3/IGSF8/LAMC1/LGALS3/PCD6IP/SFN/TPM3/VARS/YWHAZ) for mPDAC-EVs and 9 (ACTB/ALDH2/GAPDH/HNRNPA2B/ITGA2/NEXN/PKM/RPN1/S100A6) for KPC-EVs were significantly overexpressed in tumor tissues according to gene expression profiling interaction analysis (GEPIA). Concerning the potential clinical relevance of these data, the cluster of ACTB, ITGA2, GAPDH and PKM genes displayed an adverse effect (p < 0.05) on the overall survival of PDAC patients.
Authors
- José L. Cohen (ORCID: https://orcid.org/0000-0002-5077-6726)
- Damien Habert
- Benedetta Ferrara (ORCID: https://orcid.org/0000-0002-2569-5115)
- Alba Nicolás‐Boluda (ORCID: https://orcid.org/0000-0002-3029-8755)
- Isidora Simanic
- Michel Sève (ORCID: https://orcid.org/0000-0001-5503-9488)
- Benoît Vingert (ORCID: https://orcid.org/0000-0003-4156-2504)
- Flavia Castellano (ORCID: https://orcid.org/0000-0001-9389-6704)
- Ilaria Cascone (ORCID: https://orcid.org/0000-0003-4903-8926)
- Sandrine Bourgoin‐Voillard (ORCID: https://orcid.org/0000-0001-6511-0612)
- Florence Gazeau (ORCID: https://orcid.org/0000-0002-6482-3597)
- Benoît Vallée (ORCID: https://orcid.org/0009-0006-2538-9640)
- José Courty
Institutions
- Institut polytechnique de Grenoble (FR)
- Centre National de la Recherche Scientifique (FR)
- Vita-Salute San Raffaele University (IT)
- Inserm (FR)
- Université Paris-Est Créteil (FR)
- Université Paris Cité (FR)
- Université Paris-Saclay (FR)
- Centre Hospitalier Universitaire de Grenoble (FR)
- Laboratoire Matière et Systèmes Complexes (FR)
- Établissement Français du Sang (FR)
- Istituti di Ricovero e Cura a Carattere Scientifico (IT)
- Hôpital Albert-Chenevier (FR)
- Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele (IT)
- Université Grenoble Alpes (FR)
Publication Details
- Journal
- PROTEOMICS
- Published
- 2024-09-16
- DOI
- https://doi.org/10.1002/pmic.202400058
- Citations
- 3
- Primary Topic
- Extracellular vesicles in disease
- Type
- article
- Field-Weighted Citation Impact
- 0.70
Funders
- Agence Nationale de la Recherche
- Ligue Contre le Cancer
- Centre National de la Recherche Scientifique
- Institut National Du Cancer
- Université Paris-Est Créteil Val-de-Marne