Publication: COMPARISON OF PROTEOMIC PROFILES OF CONDITIONED MEDIA FROM METASTATIC PANCREATIC DUCTAL ADENOCARCINOMA CELLS (PDACS), PANCREATIC STELLATE CELLS (PSCS) AND THEIR CO-CULTURE
Date
2022
Authors
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Publisher
International Medical University
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an almost always deadly illness, and early
identification is a crucial factor in enhancing survival. The tumour microenvironment (TME),
a possible source of biomarkers in PDAC, has a significant impact in cell proliferation,
metastasis, and treatment resistance, all of which contribute to a poorer clinical outcome.
Metastatic PDAC (SW1990 cell line) and pancreatic stellate cells (PSCs), one of the major cell
types that comprise the tumour microenvironment (TME) of pancreatic cancer, foster an
immunosuppressive environment around the tumour. The purpose of this investigation was to
examine the proteome profiles of conditioned media (CM) from PSCs, SW1990, and
PSC+SW1990 co-culture. To establish the probable proteins responsible for the different
immunosuppressive efficacy of PSCs, SW1990, and PSC+SW1990 co-culture, the CM
containing the secreted proteins from all 3 cell line groups were analysed by Liquid
Chromatography with tandem Mass Spectrometry (LC-MS/MS) and then subjected to
bioinformatics analysis, including identification of differentially expressed proteins (DEPs),
Gene Ontology (GO) terms analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG)
enrichment pathway. TGM2, KRT8, KRT18, KRT19, MYH9, NME1, NME1-NME2, and
LDHA were the eight DEPs that were significantly elevated in all three cell line groups
comparisons with a false discovery rate (FDR) 0.05 and fold change (FC) ≥ 2. Multiple
signalling pathways, including oestrogen signalling, actin cytoskeleton, protein processing in
endoplasmic reticulum, vascular smooth muscle contraction, the hypoxia-inducible factor 1
(HIF-1) and the central carbon metabolism, were enriched in the comparison study. The DEPs
detected, their GO terns, and the signalling pathways were integrated and matched with
literature and proteomic data from prior research in order to better comprehend their association
with PSCs and metastatic PDAC. In conclusion, this comparative proteomic research extends 3
the evidence of protein alterations linked with PSCs and metastatic PDAC that should be
studied further as possible biomarkers or therapeutic targets
Description
Keywords
Pancreatic Ducts, Adenocarcinoma, Tumor Microenvironment, Biomarkers, Pancreatic Neoplasms, Chromatography, Liquid, Mass Spectrometry