Gupta, P, Bermejo-Rodriguez, C 
ORCID: 0000-0002-7554-1640, Kocher, H, Pérez-Mancera, PA and Velliou, EG
(2024)
Chemotherapy Assessment in Advanced Multicellular 3D Models of Pancreatic Cancer: Unravelling the Importance of Spatiotemporal Mimicry of the Tumor Microenvironment.
Advanced Biology.
e2300580-.
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a challenge for global health with very low survival rate and high therapeutic resistance. Hence, advanced preclinical models for treatment screening are of paramount importance. Herein, chemotherapeutic (gemcitabine) assessment on novel (polyurethane) scaffold-based spatially advanced 3D multicellular PDAC models is carried out. Through comprehensive image-based analysis at the protein level, and expression analysis at the mRNA level, the importance of stromal cells is confirmed, primarily activated stellate cells in the chemoresistance of PDAC cells within the models. Furthermore, it is demonstrated that, in addition to the presence of activated stellate cells, the spatial architecture of the scaffolds, i.e., segregation/compartmentalization of the cancer and stromal zones, affect the cellular evolution and is necessary for the development of chemoresistance. These results highlight that, further to multicellularity, mapping the tumor structure/architecture and zonal complexity in 3D cancer models is important for better mimicry of the in vivo therapeutic response.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | 3D model, chemoresistance, gemcitabine, multicellular tumor model, pancreatic cancer, stellate cells |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 15 Feb 2024 10:55 |
| Last Modified: | 26 Feb 2024 07:56 |
| DOI: | 10.1002/adbi.202300580 |
| Open Access URL: | https://onlinelibrary.wiley.com/doi/full/10.1002/a... |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3178662 |
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