ArticleCancer cell international2025
Combined action of suicide gene exosomes from pancreatic cancer-associated fibroblasts and from mesenchymal stem cells as a pancreatic ductal adenocarcinoma treatment approach.
Article in Cancer cell international, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- The multifaceted roles of mesenchymal stem cell-derived exosomes in digestive system malignancies: mechanisms and therapeutic implications.Frontiers in cell and developmental biology · 2026Review
- Role of cancer-associated fibroblast-derived exosomes in pancreatic cancer: clinical therapeutic potential and targeting challenges.Frontiers in immunology · 2026Review
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Authors and funding
22 authors.
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Abstract
backgroundThe pancreatic cancer-associated fibroblasts (pCAFs) are among the most active components of the pancreatic ductal adenocarcinoma (PDAC). The pCAFs being of mesenchymal stem/stromal cell origin, interact directly with tumor stromal elements, modulate tumor development, and are involved in the formation of pre-metastatic niches that result in unsatisfactory PDAC treatment outcomes. This study aimed to develop an innovative approach for the treatment of desmoplastic pancreatic carcinoma via intracellularly targeted exosomes derived from pCAFs and from mesenchymal stem cells (MSCs) transduced with the suicide gene - yeast cytosine deaminase::uracil phosphoribosyl transferase (yCD::UPRT).
methodspCAFs were isolated from four PDAC tumor specimens and MSCs from various tissues. Their transduction with yCD::UPRT gene produce homogenous gene transduced cell populations capable of secreting suicide gene exosomes. Both gene- transduced and naive cells and their exosomes underwent characterization by biophysical, biochemical, microscopic, and LC-MS/MS proteomic methods. Tumor cell-killing functionality was assessed using three pancreatic cancer cell lines. The killing efficacy of combined suicide gene exosomes of MSCs and pCAFs was measured in a mixture of pCAFs and MIA PaCa-2 cells as a simulated desmoplastic pancreatic tumor in vitro.
resultsMSCs and pCAFs suicide gene exosomes act as cancer cell-targeted drugs, effectively killing pancreatic carcinoma cells. Exosomes intracellular convert the non-toxic prodrug 5-fluorocytosine into cytotoxic 5-fluorouracil and its metabolites in a dose-dependent manner. In experiments simulating the desmoplastic microenvironment of PDAC, we have found that the suicide gene exosomes from both cells conjugated with prodrug effectively target and inhibit the growth of simulated PDAC.
conclusionExosomes containing the yCD::UPRT gene from pCAFs and MSCs function as "Trojan horse" therapies, efficiently and dose-dependently eliminating pancreatic cancer cells. PDAC environment-targeted yCD::UPRT-gene exosomes from MSCs and pCAFs show promise for a novel PDAC treatment.
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