Project description:Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease. Understanding its biology is crucial for finding effective therapies. Exosomes have been implicated in cancer, but their behavior in living systems remains poorly understood. We aimed to map the spatiotemporal distribution of exosomes from both healthy pancreas and PDAC to determine their biological significance. To achieve this, we developed a genetically engineered mouse model (ExoBow) to trace spontaneous exosomes communication. Within the PDAC microenvironment, cancer cells establish preferential communication routes with cancer associated fibroblasts and endothelial cells. The latter is a conserved event in the healthy pancreas. Inhibiting exosomes secretion in both scenarios significantly enhanced angiogenesis, underscoring the contribution of exosomes to the vascularization of the organ and to cancer. Inter-organ communication is significantly increased in PDAC, and the thymus is a sustained target in both contexts. PDAC cells also communicate with the kidneys and lungs, and the healthy pancreas with bone-marrow, brain, and intestines. In sum, we found that exosomes mediate an organized communication network in vivo that controls angiogenesis locally, both in the healthy pancreas and PDAC, and that targets the thymus also in both conditions, unravelling their potential role in central immune surveillance and anti-tumor immune response.
Project description:Pancreatic cancer is a devastating disease with both local invasion and distant metastasis. Identifying the genes expressed in liver metastases and signatures of metastatic progression would therefore be of particular importance as they could aid in both recurrence prediction as well as representing novel therapeutic targets. Keywords: Gene expression profiling We have performed microarray gene expression analysis of normal pancreas, primary pancreatic ductal adenocarcinoma (PDAC), normal liver and pancreatic liver metastases to identify potential therapeutic targets.
Project description:Comparing the miRNA profile of exosomes from ASML vs ASML CD44v kd pancreatic adenocarcinoma line revealed that the expression level of 33 from the 40 most abundant miRNA differed significantly between ASMLwt and ASML-CD44vkd exosomes In this study tumor cell exosomes, deemed important for intercellular communication were analysed for their miRNA content. Exosomes from a highly metastatic pancreatic adenocarcinoma cell line, ASML and from a CD44v kd of ASML were used for RNA preparation using Trizol reagent, and the total RNA was sent to Genomics core facility,EMBL, Heidelberg for miRCURY LNA microRNA Array, v.11.0 - hsa, mmu & rno
Project description:Solid-pseudopapillary neoplasm of pancreas (SPN), ductal adenocarcinoma (PCA), neuroendocrine tumor (NET) and non-neoplastic pancreas. comparison with gene expression of tumors and non-tumors
Project description:Pancreatic cancer is a devastating disease with both local invasion and distant metastasis. Identifying the genes expressed in liver metastases and signatures of metastatic progression would therefore be of particular importance as they could aid in both recurrence prediction as well as representing novel therapeutic targets. Keywords: Gene expression profiling We have performed microarray gene expression analysis of normal pancreas, primary pancreatic ductal adenocarcinoma (PDAC), normal liver, and pancreatic liver metastases to identify potential therapeutic targets. This dataset is part of the TransQST collection.
Project description:Acinar to ductal metaplasia (ADM) occurs in the pancreas in response to tissue injury and is a potential precursor for adenocarcinoma. We perfomed scRNAseq on lineage-traced cells resulting from acinar cells upon pancreas injury.
Project description:Constitutive Kras and NF-kB activation is identified as signature alterations in human pancreatic ductal adenocarcinoma (PDAC). Here, we report that pancreas-targeted IKK2/beta inactivation inhibited NF-kB activation and completely suppressed PDAC development. Our findings demonstrated that NF-kB is required for development of pancreatic ductal adenocarcinoma that was initiated by Kras activation.
