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Verloy, R.; Privat-Maldonado, A.; Van Audenaerde, J.; Rovers, S.; Zaryouh, H.; De Waele, J.; Quatannens, D.; Peeters, D.; Roeyen, G.; Deben, C.; Smits, E.; Bogaerts, A. |
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Title |
Capturing the Heterogeneity of the PDAC Tumor Microenvironment: Novel Triple Co-Culture Spheroids for Drug Screening and Angiogenic Evaluation |
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A1 Journal Article |
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2025 |
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Cells |
Abbreviated Journal |
Cells |
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14 |
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6 |
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450 |
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Keywords |
A1 Journal Article; pancreatic ductal adenocarcinoma; triple co-culture spheroids; tumor microenvironment; drug resistance; heterogeneity; angiogenesis; in vitro 3D model; pancreatic stellate cells; endothelial cells; cancer-associated fibroblasts; Plasma, laser ablation and surface modeling Antwerp (PLASMANT) ; |
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Abstract |
Pancreatic ductal adenocarcinoma (PDAC) presents significant treatment challenges due to its desmoplastic reaction, which impedes therapeutic effectiveness, highlighting the need for advanced vitro models to better mimic the complex tumor environment. The current three-dimensional co-culture models of fibroblasts and endothelial cells are lacking, which presents a challenge for performing more comprehensive in vitro research. Our study developed triple co-culture spheroid models using MiaPaCa-2 and BxPC-3 cancer cell lines, with RLT-PSC and hPSC21 pancreatic stellate cell lines and the endothelial cell line HMEC-1. These models were assessed through growth assays, multicolor flow cytometry to optimize cell ratios, cell viability assays to evaluate drug responses, and a tube formation assay with a spheroid-conditioned medium to examine angiogenesis. Our triple co-culture spheroids effectively replicate the PDAC microenvironment, showing significant variations in drug responses influenced by cellular composition, density, and spatial arrangement. The tube formation assay showcased the potential of our models to quantitatively assess a treatment-induced angiogenic response. These cost-effective triple-co-culture in vitro spheroid models provide vital insights into the PDAC microenvironment, significantly improving the quality of the in vitro evaluation of treatment responses. |
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Publication Date |
2025-03-18 |
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2073-4409 |
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Open Access |
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Notes |
Fund for Scientific Research, 1SD6522N 1S76421N ; Research Fund of UAntwerp, FFB190245 FFB210293 FFB210425 BOF ; Dedert Schilde vzw; Willy Floren; Vereycken family; |
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Most recent IF: NA |
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Call Number |
PLASMANT @ plasmant @ |
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9395 |
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