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A Self-Assembled 3D Model Demonstrates How Stiffness Educates Tumor Cell Phenotypes and Therapy Resistance in Pancreatic Cancer.
Liu, Ying; Okesola, Babatunde O; Osuna de la Peña, David; Li, Weiqi; Lin, Meng-Lay; Trabulo, Sara; Tatari, Marianthi; Lawlor, Rita T; Scarpa, Aldo; Wang, Wen; Knight, Martin; Loessner, Daniela; Heeschen, Christopher; Mata, Alvaro; Pearce, Oliver M T.
Afiliación
  • Liu Y; Barts Cancer Institute, Queen Mary University of London, London, EC1M 6BQ, UK.
  • Okesola BO; School of Engineering and Materials Science, Queen Mary University of London, London, E1 4NS, UK.
  • Osuna de la Peña D; School of Life Sciences, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham, NG7 2RD, UK.
  • Li W; Barts Cancer Institute, Queen Mary University of London, London, EC1M 6BQ, UK.
  • Lin ML; School of Engineering and Materials Science, Queen Mary University of London, London, E1 4NS, UK.
  • Trabulo S; School of Engineering and Materials Science, Queen Mary University of London, London, E1 4NS, UK.
  • Tatari M; Barts Cancer Institute, Queen Mary University of London, London, EC1M 6BQ, UK.
  • Lawlor RT; Barts Cancer Institute, Queen Mary University of London, London, EC1M 6BQ, UK.
  • Scarpa A; Barts Cancer Institute, Queen Mary University of London, London, EC1M 6BQ, UK.
  • Wang W; Department of Diagnostics and Public Health, Section of Pathology, University of Verona, Verona, 37134, Italy.
  • Knight M; ARC-Net, Applied Research on Cancer Centre, University of Verona, Verona, 37134, Italy.
  • Loessner D; Department of Diagnostics and Public Health, Section of Pathology, University of Verona, Verona, 37134, Italy.
  • Heeschen C; ARC-Net, Applied Research on Cancer Centre, University of Verona, Verona, 37134, Italy.
  • Mata A; School of Engineering and Materials Science, Queen Mary University of London, London, E1 4NS, UK.
  • Pearce OMT; Centre for Bioengineering, School of Engineering and Materials Science, Queen Mary University of London, London, E1 4NS, UK.
Adv Healthc Mater ; 13(17): e2301941, 2024 Jul.
Article en En | MEDLINE | ID: mdl-38471128
ABSTRACT
Pancreatic ductal adenocarcinoma (PDAC) is characterized by a dense and stiff extracellular matrix (ECM) associated with tumor progression and therapy resistance. To further the understanding of how stiffening of the tumor microenvironment (TME) contributes to aggressiveness, a three-dimensional (3D) self-assembling hydrogel disease model is developed based on peptide amphiphiles (PAs, PA-E3Y) designed to tailor stiffness. The model displays nanofibrous architectures reminiscent of native TME and enables the study of the invasive behavior of PDAC cells. Enhanced tuneability of stiffness is demonstrated by interacting thermally annealed aqueous solutions of PA-E3Y (PA-E3Yh) with divalent cations to create hydrogels with mechanical properties and ultrastructure similar to native tumor ECM. It is shown that stiffening of PA-E3Yh hydrogels to levels found in PDAC induces ECM deposition, promotes epithelial-to-mesenchymal transition (EMT), enriches CD133+/CXCR4+ cancer stem cells (CSCs), and subsequently enhances drug resistance. The findings reveal how a stiff 3D environment renders PDAC cells more aggressive and therefore more faithfully recapitulates in vivo tumors.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / Células Madre Neoplásicas / Resistencia a Antineoplásicos / Hidrogeles / Matriz Extracelular / Transición Epitelial-Mesenquimal / Microambiente Tumoral Límite: Humans Idioma: En Revista: Adv Healthc Mater Año: 2024 Tipo del documento: Article Pais de publicación: Alemania
Texto completo
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / Células Madre Neoplásicas / Resistencia a Antineoplásicos / Hidrogeles / Matriz Extracelular / Transición Epitelial-Mesenquimal / Microambiente Tumoral Límite: Humans Idioma: En Revista: Adv Healthc Mater Año: 2024 Tipo del documento: Article Pais de publicación: Alemania