Project description:Genome wide DNA methylation profiling of cancer associated fibroblasts. The hypothesis tested in the present study was that tumor induced DNA methylation in cancer associated fibroblasts. Results showed DNA methlation status in cancer associated fibroblasts changed after coculture with pancreatic cancer cells.
Project description:This study used 10X Genomics, single-cell RNA-sequencing to examine the cell types present in the KrasLSL-G12D; Trp53LSL-R172H; Pdx1-Cre (KPC) mouse model for pancreatic ductal adenocarcinoma. The study analyzed tumors from 4 different mice. For each tumor, we performed flow sorting to isolate all viable cells, and to isolate a fibroblast-enriched population of cells for single-cell RNA-seq to determine the transcriptomes of individual cells in KPC pancreatic ductal adenocarcinoma tumors.
Project description:This study sought the basis for the failure of immunosurveillance in pancreatic ductal adenocarcinoma (PDA). The FAP+ cell was shown to be immunosuppressive in a spontaneous PDA model. Bioinformatic analyses show it to be identical to the Carcinoma-associated fibroblast (CAF). FAP+ cells were sorted from pancreatic ductal adenocarcinoma. Cells were isolated in duplicate experiments and these were analysed separately. These were compared separately to previously published publicly available CD4+ T-cell subset data (C57BL/6 mice and Foxp3-RFP mice (Line 8374) GEO accession GSE20898), and previously published FAP+ cell datasets (transgenic albino (Tyr-/-) C57BL/6 mouse, GEO accession GSE39438).
Project description:Analysis of cancer associated fibroblasts at gene expression level. The hypothesis tested in the present study was that tumor induced DNA methylation in cancer associated fibroblasts and thus regulated the gene expression in cancer associated fibroblasts. Results showed gene expression level in cancer associated fibroblasts changed after coculture with pancreatic cancer cells.
Project description:Perineural invasion (PNI) is a prominent characteristic of pancreatic ductal adenocarcinoma (PDAC) and indicates poor prognosis. The invasion of the surrounding nerves by pancreatic cancer cells not only provides route for metastasis but also contributes to neural remodeling and changes in the neuronal milieu that can profoundly influenced the microenvironment of pancreatic cancer. To investigate the downstream molecules associated with PNI, the experiment analyzed mRNA expression of 50 pairs of pancreatic ductal adenocarcinoma tissue and paired adjacent non-tumor tissue, among which 28 pairs of cases diagnosed with PNI by experienced pathologist. Results provide new insight into molecular basis for the influence of PNI on the microenvironment of pancreatic cancer.
Project description:Exosomes from pancreatic cancer-associated fibroblasts and mesenchymal stem cells that have been transduced with the yeast cytosine deaminase::uracil phosphoribosyl transferase release suicide gene exosomes acting as "Trojan horse" drugs, effectively killing pancreatic cancer cells by converting the non-toxic prodrug 5-fluorocytosine intracellularly into the cytotoxic 5-fluorouracil. We have shown in experiments in vitro, involving a simulated desmoplastic pancreatic tumor, that the combined action of these targeted exosomes could be an approach for pancreatic ductal adenocarcinoma treatment.
Project description:Pancreatic ductal adenocarcinoma (PDAC) continues to carry a dismal prognosis. The disease is characterized by a uniquely dense fibrotic matrix generated by cancer-associated fibroblasts (CAFs). We have previously demonstrated that fibroblast-driven chronic inflammation suppresses T cell function through a MYD88-dependent mechanism. While extensively studied in myeloid cells, the role of MYD88 signaling in CAFs and its effects on PDAC remain poorly understood. In this study, we identify a MYD88-driven inflammatory CAF population in PDAC using a combination of bulk, single-cell, and spatial transcriptomic studies. Using an innovative collagen gel implantation model, we demonstrate that loss of MYD88 in CAFs enhances T cell infiltration and suppresses tumor growth. Combining MYD88 inhibition with immune checkpoint blockade significantly reduces tumor size and enhances antitumor immune responses, underscoring its potential as a therapeutic target in PDAC.
Project description:Pancreatic ductal adenocarcinoma (PDAC) continues to carry a dismal prognosis. The disease is characterized by a uniquely dense fibrotic matrix generated by cancer-associated fibroblasts (CAFs). We have previously demonstrated that fibroblast-driven chronic inflammation suppresses T cell function through a MYD88-dependent mechanism. While extensively studied in myeloid cells, the role of MYD88 signaling in CAFs and its effects on PDAC remain poorly understood. In this study, we identify a MYD88-driven inflammatory CAF population in PDAC using a combination of bulk, single-cell, and spatial transcriptomic studies. Using an innovative collagen gel implantation model, we demonstrate that loss of MYD88 in CAFs enhances T cell infiltration and suppresses tumor growth. Combining MYD88 inhibition with immune checkpoint blockade significantly reduces tumor size and enhances antitumor immune responses, underscoring its potential as a therapeutic target in PDAC.
Project description:Pancreatic adenocarcinoma is one of the most aggressive human cancers and displays many different chromosomal abnormalities and mutations. By using 244K high-resolution array-comparative genomic hybridization (aCGH) we studied the genome alterations of 39 fine-needle aspirations from pancreatic adenocarcinoma and 9 human adenocarcinoma pancreatic cell lines.