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Profiling of Kallikrein Proteases and Global Proteome Biology of PDAC, Chronic Pancreatitis and Normal Pancreas

ABSTRACT: Cell conditioned medium from human pancreatic cancer cell lines MiaPaCa-2, AsPC-1, primary pancreatic cell lines as well as human FFPE tissue samples from pancreatic ductal adenocarcinoma (PDAC), chronic pancreatitis (CP), ampullary cancer, non-malignant adjacent pancreas and normal pancreas were analyzed via targeted (SRM, PRM) and/or explorative (DIA) mass spectrometry.

INSTRUMENT(S): TSQ Vantage, Q Exactive Plus

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Prof. Oliver Schilling

PROVIDER: MSV000090255 | MassIVE |

REPOSITORIES: MassIVE

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Targeted and explorative profiling of kallikrein proteases and global proteome biology of pancreatic ductal adenocarcinoma, chronic pancreatitis, and normal pancreas highlights disease-specific proteome remodelling.

Werner Janina J Bernhard Patrick P Cosenza-Contreras Miguel M Pinter Niko N Fahrner Matthias M Pallavi Prama P Eberhard Johannes J Bronsert Peter P Rückert Felix F Schilling Oliver O

Neoplasia (New York, N.Y.) 20230105

Pancreatic ductal adenocarcinoma (PDAC) represents one of the most aggressive and lethal malignancies worldwide with an urgent need for new diagnostic and therapeutic strategies. One major risk factor for PDAC is the pre-indication of chronic pancreatitis (CP), which represents highly inflammatory pancreatic tissue. Kallikreins (KLKs) are secreted serine proteases that play an important role in various cancers as components of the tumor microenvironment. Previous studies of KLKs in solid tumors ...[more]

PMID: 36610378

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Disease associated fibroblasts from various pancreatic disorders exhibit subtype specific genetic profile [miRNA]

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Methylated DNA immunoprecipitation coupled with NimbleGen's array to identify methylated genes in pancreatic ductal adenocarcinoma

Project description:Pancreatic ductal adenocarcinoma (PDAC) is a highly invasive cancer with a poor prognosis. Using methylated DNA immunoprecipitation (MeDIP)-chip analysis, we found that 161 genes that were specifically hypermethylated in PANC-1 cells. Among them, miR-615-5p was hypermethylated in its putative promoter region, which silenced its expression in PDAC cell lines. Comparison between PANC-1 cell lines and normal pancreas tissue

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Expression data from human pancreatic cancer cell lines and mouse orthotopic tumors generated using human PDAC cell lines replete and depleted for RBFOX2

Project description:RBFOX2 is an RNA binding protein that directs alternative splicing. In this study, we characterized RBFOX2-mediated alternative splicing in pancreatic cancer (PDAC) In this dataset, we assayed gene-level and exon-level expression differences in pancreatic cancer cell lines replete and depleted for RBFOX2 expression and in 8 pairs of orthotopic pancreas tumors and related liver metastases generated from human 4039 or Panc1 cell lines replete or depleted for RBFOX2.

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Single-cell transcriptomic analysis of mouse pancreas: characteristic features of pancreatic ductal cells in chronic pancreatitis

Project description:Chronic pancreatitis (CP) is a pathogenically complex fibro-inflammatory disorder of the pancreas. Our understanding of CP pathogenesis is partly limited by the incomplete characterization of pancreatic cell types. Here, we performed single-cell RNA sequencing on 3,386 cells from the pancreas of one control mouse and mice with caerulein-induced CP. These data provides a preliminary description of the single-cell transcriptome profiles of mouse pancreata and accurately demonstrates the characteristics of pancreatic ductal cells in CP.

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Project description:A subset of human pancreatic ductal adenocarcinoma cells (PDACs) is characterized by high Fosl1 expression and Fosl1 is linked to the control of pro-inflammatory pathways and growth of PDAC cells. To mimick the human disease in mice (> 90% of PDAC patients harbour Kras mutations) the mutated LSL-KrasG12D allele was combined with the pancreas specific Cre recombinase Ptf1aCre (p48Cre). The two pancreatic cancer cell lines (Ptf1aCre, LSL-KrasG12D/+) were isolated from these mice and used for transcriptomics studies. The two different murine pancreatic cancer cell lines (Ptf1aCre, LSL-KrasG12D) were treated with two different Fosl1 siRNAs and one control siRNA, each. 72h after transfection a sufficient knockdown was tested by immunoblotting and qPCR. Total mRNA was isolated and checked for integrity. According to manufacture's recommendation the samples were subjected to microarray analysis using the Affymetrix Mouse Gene ST 1.0 array chip to discover differentially expressed genes.

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