Gupta, Priyanka;
Bermejo-Rodriguez, Camino;
Kocher, Kemant;
Pérez- Mancera, Pedro A;
Velliou, Eirini G;
(2024)
Chemotherapy Assessment in Advanced Multicellular 3D
Models of Pancreatic Cancer: Unravelling the Importance of
Spatiotemporal Mimicry of the Tumor Microenvironment.
Advanced Biology
, Article 2300580. 10.1002/adbi.202300580.
(In press).
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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.
| Type: | Article |
|---|---|
| Title: | Chemotherapy Assessment in Advanced Multicellular 3D Models of Pancreatic Cancer: Unravelling the Importance of Spatiotemporal Mimicry of the Tumor Microenvironment |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/adbi.202300580 |
| Publisher version: | https://doi.org/10.1002/adbi.202300580 |
| Language: | English |
| Additional information: | Copyright © 2024 The Authors. Advanced Biology published by Wiley-VCH GmbH This is an open access article under the terms of the Creative Commons Attribution License,https://creativecommons.org/licenses/by/4.0/, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | 3D model, chemoresistance, gemcitabine, multicellular tumor model, pancreatic cancer, stellate cells |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Targeted Intervention |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10186091 |
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