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CA19-9-positive extracellular vesicles are the risk for cancer-associated thrombosis in pancreatic cancer

ABSTRACT: To investigate the effect of pancreatic cancer cell-derived EVs on HUVEC, we performed gene expression analysis of HUVEC treated with or without EVs for 5h.

ORGANISM(S): Homo sapiens

PROVIDER: GSE227567 | GEO | 2024/08/01

REPOSITORIES: GEO

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CA19-9-Positive Extracellular Vesicle Is a Risk Factor for Cancer-Associated Thrombosis in Pancreatic Cancer.

Project description:Background and aimsCancer-associated venous thromboembolism (VTE) is a frequent complication associated with high mortality in patients with cancer, particularly pancreatic cancer. While biological factors such as coagulation factors released from cancer cells may underlie the mechanisms of cancer-associated VTE, the detailed mechanisms have not been determined. Here, we aimed to determine whether extracellular vesicles carrying a glycan sialyl-Lewisa, known as carbohydrate antigen 19-9 (CA19-9), which is a clinically used serum tumor marker and selectin ligand, are a significant cause of cancer-associated VTE.MethodsRisk factors for cancer-associated VTE were determined using clinical data. EVs derived from CA19-9-deficient or overexpressing pancreatic cancer cells were characterized. The protein levels of coagulation factors on the surface of the EVs were quantified using our newly developed sensitive method.ResultsHigher CA19-9 levels in the sera of patients were significantly associated with the occurrence of VTE. Using CA19-9-negative or overexpressing pancreatic cancer cells, we found that EVs derived from these cells interacted with E-selectin of endothelial cells in a CA19-9-dependent manner in cell-based assays and in vitro blood vessel models. EVs derived from cancer cells have higher tissue factor levels on their surfaces, and increased tissue factor activity is induced locally, where CA19-9-positive EVs bind to activated endothelial cells.ConclusionThese results suggest that the binding between CA19-9-positive EVs released from cancer cells and endothelial cell E-selectin explains the increased frequency of VTE in patients with pancreatic cancer.

| S-EPMC11308089 | biostudies-literature

microRNA expression profile in isolated human pancreatic islets and in human pancreatic islet-derived extracellular vesicles -EVs-

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CA19-9-positive extracellular vesicles are the risk for cancer-associated thrombosis in pancreatic cancer

Project description:CA19-9-positive extracellular vesicles are the risk for cancer-associated thrombosis in pancreatic cancer

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Transcriptome reprogramming of CD11b+ bone marrow cells by pancreatic cancer extracellular vesicles

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Effects of prostate cancer patient urinary extracellular vesicles and hypoxic extracellular vesicles from prostate cancer cell lines on the transcriptomes of cancer-associated and normal fibroblasts

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Project description:Pancreatic ductal adenocarcinoma (PDAC) tumours carry multiple gene mutations and respond poorly to treatments. There is currently an unmet need for drug carriers that can deliver multiple gene cargoes to high solid tumour burden like PDAC. Here, we report a dual-targeted extracellular vesicle (EV) carrying high loads of RNA that effectively suppresses large PDAC tumours in mice. The EV surface contains a CD64 protein that has a tissue targeting peptide and a humanized monoclonal antibody. Cells sequentially transfected with plasmid DNAs encoding for the RNA and protein of interest by Transwell®-based asymmetric cell electroporation released abundant targeted EVs with high RNA loading. Together with a low dose chemotherapy drug, Gemcitabine, dual-targeted EVs effectively suppressed large orthotopic PANC-1 and patient derived xenograft tumours in mice and extended animal survival. This work presents a clinically accessible and scalable way to produce abundant EVs for delivering multiple gene cargoes to large solid tumours.

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miRNA expression of extracellular vesicles

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