Physico-chemical characterization of the tumour microenvironment of pancreatic ductal adenocarcinoma

Elena García-Gareta; Alejandro Calderón-Villalba; Pilar Alamán-Díez; Carlos Gracia Costa; Pedro Enrique Guerrero; Carlota Mur; Ana Rueda Flores; Nerea Olivera Jurjo; Patricia Sancho; María Ángeles Pérez; José Manuel García-Aznar

doi:10.1016/j.ejcb.2024.151396

Physico-chemical characterization of the tumour microenvironment of pancreatic ductal adenocarcinoma

Eur J Cell Biol. 2024 Feb 12;103(2):151396. doi: 10.1016/j.ejcb.2024.151396. Online ahead of print.

Affiliations

¹ Multiscale in Mechanical & Biological Engineering Research Group, Aragon Institute of Engineering Research (I3A), School of Engineering & Architecture, University of Zaragoza, Zaragoza, Aragon, Spain; Aragon Institute for Health Research (IIS Aragon), Miguel Servet University Hospital, Zaragoza, Aragon, Spain; Division of Biomaterials & Tissue Engineering, UCL Eastman Dental Institute, University College London, London, United Kingdom. Electronic address: garciage@unizar.es.
² Multiscale in Mechanical & Biological Engineering Research Group, Aragon Institute of Engineering Research (I3A), School of Engineering & Architecture, University of Zaragoza, Zaragoza, Aragon, Spain.
³ Aragon Institute of Engineering Research (I3A), School of Engineering & Architecture, University of Zaragoza, Zaragoza, Aragon, Spain.
⁴ Aragon Institute for Health Research (IIS Aragon), Miguel Servet University Hospital, Zaragoza, Aragon, Spain.
⁵ Multiscale in Mechanical & Biological Engineering Research Group, Aragon Institute of Engineering Research (I3A), School of Engineering & Architecture, University of Zaragoza, Zaragoza, Aragon, Spain; Aragon Institute for Health Research (IIS Aragon), Miguel Servet University Hospital, Zaragoza, Aragon, Spain.

PMID: 38359522
DOI: 10.1016/j.ejcb.2024.151396

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive lethal malignancy that accounts for more than 90% of pancreatic cancer diagnoses. Our research is focused on the physico-chemical properties of the tumour microenvironment (TME), including its tumoural extracellular matrix (tECM), as they may have an important impact on the success of cancer therapies. PDAC xenografts and their decellularized tECM offer a great material source for research in terms of biomimicry with the original human tumour. Our aim was to evaluate and quantify the physico-chemical properties of the PDAC TME. Both cellularized (native TME) and decellularized (tECM) patient-derived PDAC xenografts were analyzed. A factorial design of experiments identified an optimal combination of factors for effective xenograft decellularization. Our results provide a complete advance in our understanding of the PDAC TME and its corresponding stroma, showing that it presents an interconnected porous architecture with very low permeability and small pores due to the contractility of the cellular components. This fact provides a potential therapeutic strategy based on the therapeutic agent size.

Keywords: Biological bioreactor; Decellularization; Pancreatic ductal adenocarcinoma; Physico-chemical properties; Tumour microenvironment; Xenograft.