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

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

Resumen: 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.

Idioma: Inglés

DOI: 10.1016/j.ejcb.2024.151396

Año: 2024

Publicado en: European Journal of Cell Biology 103, 2 (2024), 151396 [16 pp.]
ISSN: 0171-9335

Financiación: info:eu-repo/grantAgreement/ES/DGA/LMP29-21
Financiación: info:eu-repo/grantAgreement/EC/H2020/101018587/EU/Individual and Collective Migration of the Immune Cellular System/ICoMICS
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI17-00082
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI20-00921
Financiación: info:eu-repo/grantAgreement/ES/MICINN/PID2020-113819RB-I00/AEI/10.13039/501100011033
Financiación: info:eu-repo/grantAgreement/ES/MICINN/RYC2021-033490-I
Financiación: info:eu-repo/grantAgreement/ES/MINECO-AEI-FEDER/PID2021-122409OB-C21
Financiación: info:eu-repo/grantAgreement/ES/MS-ISCIII-FSE/CP16-00121

Tipo y forma: Article (Published version)

Área (Departamento): Área Ingeniería Química (Dpto. Ing.Quím.Tecnol.Med.Amb.)
Área (Departamento): Área Bioquímica y Biolog.Mole. (Dpto. Bioq.Biolog.Mol. Celular)
Área (Departamento): Área Mec.Med.Cont. y Teor.Est. (Dpto. Ingeniería Mecánica)
Área (Departamento): Área Cienc.Mater. Ingen.Metal. (Dpto. Ciencia Tecnol.Mater.Fl.)