Matrix stiffness regulates the protein profile of extracellular vesicles of pancreatic cancer cell lines

Benedetta Ferrara , Sandrine Bourgoin‐voillard (1) , Damien Habert , Benoit Vallée , Alba Nicolas‐boluda (2) , Isidora Simanic , Michel Seve (1) , Benoit Vingert , Florence Gazeau (2) , Flavia Castellano , José Cohen , José Courty , Ilaria Cascone

1 TIMC - Translational Innovation in Medicine and Complexity / Recherche Translationnelle et Innovation en Médecine et Complexité - UMR 5525
2 MSC - Matière et Systèmes Complexes

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 E 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

Mots clés: ADP; adenosine 5′-diphosphate BP; biological processes CAF; cancer associated fibroblast DEP; deregulated protein ECM; extracellular matrix EV; extracellular vesicle FC; fold change GEPIA; gene expression profiling interaction analysis GO; gene ontology HIF-1; hypoxia-inducible factor-1 ITGA2; integrin alpha-2 LC; liquid chromatography MS; mass spectrometry PDAC; pancreatic ductal adenocarcinoma PDMS; polydimethylsiloxane PEP; phosphoenolpyruvate TAM; tumor associated macrophage TCA; tricarboxylic acid cycle TCGA; cancer genome atlas YM; Young's modulus extracellular vesicles; matrix; pancreatic cancer; proteomics; stiffness; adenosine 5′-diphosphate; BP; biological processes; CAF; cancer associated fibroblast; DEP; deregulated protein; ECM; extracellular matrix; EV; extracellular vesicle; FC; fold change; GEPIA; gene expression profiling interaction analysis; GO; gene ontology; HIF-1; hypoxia-inducible factor-1; ITGA2; integrin alpha-2; LC; liquid chromatography; MS; mass spectrometry; PDAC; pancreatic ductal adenocarcinoma; PDMS; polydimethylsiloxane; PEP; phosphoenolpyruvate; TAM; tumor associated macrophage; TCA; tricarboxylic acid cycle; TCGA; cancer genome atlas; YM

Domaines: Sciences du Vivant [q-bio]

Benedetta Ferrara, Sandrine Bourgoin‐voillard, Damien Habert, Benoit Vallée, Alba Nicolas‐boluda, et al.. Matrix stiffness regulates the protein profile of extracellular vesicles of pancreatic cancer cell lines. Proteomics, 2024, ⟨10.1002/pmic.202400058⟩. ⟨hal-04834740⟩