Matrix stiffness regulates the protein profile of extracellular vesicles of pancreatic cancer cell lines
Résumé
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
- integrin alpha-2
- deregulated protein
- ITGA2
- hypoxia-inducible factor-1
- HIF-1
- gene ontology
- GO
- gene expression profiling interaction analysis
- GEPIA
- fold change
- FC
- extracellular vesicle
- EV
- extracellular matrix
- ECM
- YM
- 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
- extracellular matrix EV
- mass spectrometry PDAC
- liquid chromatography MS
- integrin alpha-2 LC
- hypoxia-inducible factor-1 ITGA2
- gene ontology HIF-1
- gene expression profiling interaction analysis GO
- fold change GEPIA
- extracellular vesicle FC
- pancreatic ductal adenocarcinoma PDMS
- deregulated protein ECM
- cancer associated fibroblast DEP
- biological processes CAF
- adenosine 5′-diphosphate BP
- ADP
- DEP
- 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
Domaines
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