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pmid:35406724
Proteomics Approach Highlights Early Changes in Human Fibroblasts-Pancreatic Ductal Adenocarcinoma Cells Crosstalk.
Verena Damiani · Maria Concetta Cufaro · Maurine Fucito · Beatrice Dufrusine · Claudia Rossi · Piero Del Boccio · Luca Federici · Maria Caterina Turco · Michele Sallese · Damiana Pieragostino · Vincenzo De Laurenzi
Cells · 2022 doi:10.3390/cells11071160
Paper
complete
Experiment
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Data
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Analysis
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Execution
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Complete file
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Non-specific symptoms, lack of biomarkers in the early stages, and drug resistance due to the presence of a dense fibrous stroma all contribute to the poor outcome of this disease. The extracellular matrix secreted by activated fibroblasts contributes to the desmoplastic tumor microenvironment formation. Given the importance of fibroblast activation in PDAC pathology, it is critical to recognize the mechanisms involved in the transformation of normal fibroblasts in the early stages of tumorigenesis. To this aim, we first identified the proteins released from the pancreatic cancer cell line MIA-PaCa2 by proteomic analysis of their conditioned medium (CM). Second, normal fibroblasts were treated with MIA-PaCa2 CM for 24 h and 48 h and their proteostatic changes were detected by proteomics. Pathway analysis indicated that treated fibroblasts undergo changes compatible with the activation of migration, vasculogenesis, cellular homeostasis and metabolism of amino acids and reduced apoptosis. These biological activities are possibly regulated by ITGB3 and TGFB1/2 followed by SMAD3, STAT3 and BAG3 activation. In conclusion, this study sheds light on the crosstalk between PDAC cells and associated fibroblasts. Data are available via ProteomeXchange with identifier PXD030974.", "claims": [{"id": "claim-method", "statement": "Moreover, in order to define the differential proteins significantly expressed between the HDF cells or supernatants exposed to MIA-PaCa2 CM or DMEM SF at 24 h or 48 h, a univariate statistical analysis was performed with a p-value threshold of 0.05, visualizing results as a Volcano Plot.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35406724", "locator": "sections[7] \"2.5. 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