Capturing the Heterogeneity of the PDAC Tumor Microenvironment: Novel Triple Co-Culture Spheroids for Drug Screening and Angiogenic Evaluation

Bibliographic Details
Title: Capturing the Heterogeneity of the PDAC Tumor Microenvironment: Novel Triple Co-Culture Spheroids for Drug Screening and Angiogenic Evaluation
Authors: Ruben Verloy, Angela Privat-Maldonado, Jonas Van Audenaerde, Sophie Rovers, Hannah Zaryouh, Jorrit De Waele, Delphine Quatannens, Dieter Peeters, Geert Roeyen, Christophe Deben, Evelien Smits, Annemie Bogaerts
Source: Cells, Vol 14, Iss 6, p 450 (2025)
Publisher Information: MDPI AG, 2025.
Publication Year: 2025
Collection: LCC:Cytology
Subject Terms: pancreatic ductal adenocarcinoma, triple co-culture spheroids, tumor microenvironment, drug resistance, heterogeneity, angiogenesis, Cytology, QH573-671
More Details: 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.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 14060450
2073-4409
Relation: https://www.mdpi.com/2073-4409/14/6/450; https://doaj.org/toc/2073-4409
DOI: 10.3390/cells14060450
Access URL: https://doaj.org/article/d9f6ea6979fb42eb89d28d5655be3ecb
Accession Number: edsdoj.9f6ea6979fb42eb89d28d5655be3ecb
Database: Directory of Open Access Journals
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More Details
ISSN:14060450
20734409
DOI:10.3390/cells14060450
Published in:Cells
Language:English