Your browser doesn't support javascript.
loading
Modeling the mechanical stiffness of pancreatic ductal adenocarcinoma.
Kpeglo, Delanyo; Hughes, Matthew D G; Dougan, Lorna; Haddrick, Malcolm; Knowles, Margaret A; Evans, Stephen D; Peyman, Sally A.
Afiliación
  • Kpeglo D; Molecular and Nanoscale Physics Group, School of Physics and Astronomy, University of Leeds, LS2 9 JT, UK.
  • Hughes MDG; Molecular and Nanoscale Physics Group, School of Physics and Astronomy, University of Leeds, LS2 9 JT, UK.
  • Dougan L; Astbury Centre for Structural Molecular Biology, University of Leeds, LS2 9JT, UK.
  • Haddrick M; Molecular and Nanoscale Physics Group, School of Physics and Astronomy, University of Leeds, LS2 9 JT, UK.
  • Knowles MA; Astbury Centre for Structural Molecular Biology, University of Leeds, LS2 9JT, UK.
  • Evans SD; Medicines Discovery Catapult, Block 35, Mereside Alderley Park, Alderley Edge, SK10 4TG, UK.
  • Peyman SA; Leeds Institute of Medical Research at St James's (LIMR), School of Medicine, University of Leeds, LS2 9 JT, UK.
Matrix Biol Plus ; 14: 100109, 2022 Jun.
Article en En | MEDLINE | ID: mdl-35399702
Despite improvements in the understanding of disease biology, pancreatic ductal adenocarcinoma (PDAC) remains the most malignant cancer of the pancreas. PDAC constitutes ∼95% of all pancreatic cancers, and it is highly resistant to therapeutics. The increased tissue rigidity, which stems from the rich fibrotic stroma in the tumor microenvironment, is central to disease development, physiology, and resistance to drug perfusion. Pancreatic stellate cells (PSCs) are responsible for overproduction of extracellular matrix in the fibrotic stroma, and this is exacerbated by the overexpression of transforming growth factor-ß (TGF-ß). However, there are few in vitro PDAC models, which include both PSCs and TGF-ß or mimic in vivo-like tumor stiffness. In this study, we present a three-dimensional in vitro PDAC model, which includes PSCs and TGF-ß, and recapitulates PDAC tissue mechanical stiffness. Using oscillatory shear rheology, we show the mechanical stiffness of the model is within range of the PDAC tissue stiffness by day 21 of culture and highlight that the matrix environment is essential to adequately capture PDAC disease. PDAC is a complex, aggressive disease with poor prognosis, and biophysically relevant in vitro PDAC models, which take into account tissue mechanics, will provide improved tumor models for effective therapeutic assessment.
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Matrix Biol Plus Año: 2022 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Matrix Biol Plus Año: 2022 Tipo del documento: Article Pais de publicación: Países Bajos