Chemotherapy Assessment in Advanced Multicellular 3D Models of Pancreatic Cancer: Unravelling the Importance of Spatiotemporal Mimicry of the Tumor Microenvironment

Author:

Gupta Priyanka1,Bermejo‐Rodriguez Camino2,Kocher Hemant3,Pérez‐Mancera Pedro A.2,Velliou Eirini G.1ORCID

Affiliation:

1. Centre for 3D Models of Health and Disease Division of Surgery and Interventional Science University College London London W1W 7TY UK

2. Department of Molecular and Clinical Cancer Medicine University of Liverpool Ashton Street Liverpool L69 3GE UK

3. Centre for Tumour Biology and Experimental Cancer Medicine Barts Cancer Institute Queen Mary University of London London EC1M 6BQ UK

Abstract

AbstractPancreatic 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.

Funder

Medical Research Council

National Centre for the Replacement Refinement and Reduction of Animals in Research

Publisher

Wiley

Reference122 articles.

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