title: Optimum 3D Matrix Stiffness for Maintenance of Cancer Stem Cells Is Dependent on Tissue Origin of Cancer Cells.
abstract: BACKGROUND
  The growth and expression of cancer stem cells (CSCs) depend on many factors in the tumor microenvironment. The objective of this work was to investigate the effect of cancer cells' tissue origin on the optimum matrix stiffness for CSC growth and marker expression in a model polyethylene glycol diacrylate (PEGDA) hydrogel without the interference of other factors in the microenvironment.
  
  
  METHODS
  Human MCF7 and MDA-MB-231 breast carcinoma, HCT116 colorectal and AGS gastric carcinoma, and U2OS osteosarcoma cells were used. The cells were encapsulated in PEGDA gels with compressive moduli in the 2-70 kPa range and optimized cell seeding density of 0.6x106 cells/mL. Micropatterning was used to optimize the growth of encapsulated cells with respect to average tumorsphere size. The CSC sub-population of the encapsulated cells was characterized by cell number, tumorsphere size and number density, and mRNA expression of CSC markers.
  
  
  RESULTS
  The optimum matrix stiffness for growth and marker expression of CSC sub-population of cancer cells was 5 kPa for breast MCF7 and MDA231, 25 kPa for colorectal HCT116 and gastric AGS, and 50 kPa for bone U2OS cells. Conjugation of a CD44 binding peptide to the gel stopped tumorsphere formation by cancer cells from different tissue origin. The expression of YAP/TAZ transcription factors by the encapsulated cancer cells was highest at the optimum stiffness indicating a link between the Hippo transducers and CSC growth. The optimum average tumorsphere size for CSC growth and marker expression was 50 μm.
  
  
  CONCLUSIONS
  The marker expression results suggest that the CSC sub-population of cancer cells resides within a niche with optimum stiffness which depends on the cancer cells' tissue origin.
authors.affiliation: Biomimetic Materials and Tissue Engineering Laboratory, Department of Chemical Engineering, University of South Carolina, Columbia, SC, 29208, United States of America.
authors.forename: Esmaiel
authors.initials: E
authors.lastname: Jabbari
authors.affiliation: Biomimetic Materials and Tissue Engineering Laboratory, Department of Chemical Engineering, University of South Carolina, Columbia, SC, 29208, United States of America.
authors.forename: Samaneh K
authors.initials: SK
authors.lastname: Sarvestani
authors.affiliation: Biomimetic Materials and Tissue Engineering Laboratory, Department of Chemical Engineering, University of South Carolina, Columbia, SC, 29208, United States of America.
authors.forename: Leily
authors.initials: L
authors.lastname: Daneshian
authors.affiliation: Biomimetic Materials and Tissue Engineering Laboratory, Department of Chemical Engineering, University of South Carolina, Columbia, SC, 29208, United States of America.
authors.forename: Seyedsina
authors.initials: S
authors.lastname: Moeinzadeh
mesh_terms: D002452:Cell Count; D045744:Cell Line, Tumor / Q000502:physiology; D005434:Flow Cytometry; D045325:HCT116 Cells / Q000502:physiology; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D015151:Immunoblotting; D061986:MCF-7 Cells / Q000502:physiology; D014411:Neoplastic Stem Cells / Q000502:physiology*; D012516:Osteosarcoma / Q000503:physiopathology; D011092:Polyethylene Glycols; D060888:Real-Time Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000503:physiopathology; D059016:Tumor Microenvironment / Q000502:physiology
chemical_list: C437167:poly(ethylene glycol)diacrylate; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011092:Polyethylene Glycols