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Interfacial Curvature in Confined Coculture Directs Stromal Cell Activity with Spatial Corralling of Pancreatic Cancer Cells.
Nemec, Stephanie; Lam, Joey; Zhong, Jingxiao; Heu, Celine; Timpson, Paul; Li, Qing; Youkhana, Janet; Sharbeen, George; Phillips, Phoebe A; Kilian, Kristopher A.
Afiliación
  • Nemec S; School of Materials Science and Engineering, UNSW Sydney, Sydney, NSW, 2052, Australia.
  • Lam J; School of Chemistry Australian Centre for Nanomedicine, UNSW Sydney, Sydney, NSW, 2052, Australia.
  • Zhong J; School of Aerospace, Mechanical and Mechatronic Engineering, The University of Sydney, Sydney, NSW, 2006, Australia.
  • Heu C; Biomedical Imaging Facility, Mark Wainwright Analytical Center, UNSW Sydney, Sydney, NSW, 2052, Australia.
  • Timpson P; The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, 2052, Australia.
  • Li Q; School of Aerospace, Mechanical and Mechatronic Engineering, The University of Sydney, Sydney, NSW, 2006, Australia.
  • Youkhana J; Pancreatic Cancer Translational Research Group, Lowy Cancer Research Centre, School of Medical Sciences, UNSW Sydney, Sydney, NSW, 2052, Australia.
  • Sharbeen G; Pancreatic Cancer Translational Research Group, Lowy Cancer Research Centre, School of Medical Sciences, UNSW Sydney, Sydney, NSW, 2052, Australia.
  • Phillips PA; Pancreatic Cancer Translational Research Group, Lowy Cancer Research Centre, School of Medical Sciences, UNSW Sydney, Sydney, NSW, 2052, Australia.
  • Kilian KA; School of Materials Science and Engineering, UNSW Sydney, Sydney, NSW, 2052, Australia.
Adv Biol (Weinh) ; 5(6): e2000525, 2021 06.
Article en En | MEDLINE | ID: mdl-33754491
Interfacial cues in the tumor microenvironment direct the activity and assembly of multiple cell types. Pancreatic cancer, along with breast and prostate cancers, is enriched with cancer-associated fibroblasts (CAFs) that activate to coordinate the deposition of the extracellular matrix, which can comprise over 90% of the tumor mass. While it is clear that matrix underlies the severity of the disease, the relationship between stromal-tumor cell assembly and cell-matrix dynamics remains elusive. Micropatterned hydrogels deconstruct the interplay between matrix stiffness and geometric confinement, guiding heterotypic cell populations and matrix assembly in pancreatic cancer. Interfacial cues at the perimeter of microislands guide CAF migration and direct cancer cell assembly. Computational modeling shows curvature-stress dependent cellular localization for cancer and CAFs in coculture. Regions of convex curvature enhance edge stress that activates a myofibroblast phenotype in the CAFs with migration and increased collagen I deposition, ultimately leading to a central "corralling" of cancer cells. Inhibiting mechanotransduction pathways decreases CAF activation and the associated corralling phenotype. Together, this work reveals how interfacial biophysical cues underpin aspects of stromal desmoplasia, a hallmark of disease severity and chemoresistance in the pancreatic, breast, and prostate cancers, thereby providing a tool to expand stroma-targeting therapeutic strategies.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / Fibroblastos Asociados al Cáncer Límite: Humans / Male Idioma: En Revista: Adv Biol (Weinh) Año: 2021 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Alemania
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / Fibroblastos Asociados al Cáncer Límite: Humans / Male Idioma: En Revista: Adv Biol (Weinh) Año: 2021 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Alemania