title: Three-dimensional constructs using hyaluronan cell carrier as a tool for the study of cancer stem cells.
abstract: BACKGROUND
  Cancer research focuses increasingly on cancer stem cell study as those cells are thought to be the root of chemo and radioresistance of the most aggressive cancer types. Nevertheless, two-dimensional (2D) cell culture and even three-dimensional (3D) spheroid models, with their limited ability to reflect cell-extracellular matrix interactions, are not ideal for the study of cancer stem cells (CSCs). In this study, we establish a 3D in vitro cancer model using a synthetic and natural scaffold with tunable features and show that U87 cells cultured in this system acquire a stem-cell like phenotype.
  
  
  METHODS
  U87 astrocytoma cells were grown on polycaprolactone (PCL)-2D flat substrates (2D) and PCL-3D scaffolds (3D) eventually containing hyaluronic acid (3D-HA). Cell viability, growth patterns, morphology, and cell surface marker expression (CD44, RHAMM and CD133) were studied to assess the effect of 3D culture and presence of HA.
  
  
  RESULTS
  3D scaffold, but most prominently presence of HA induced changes in cell morphology and marker expression; 3D-HA cultures showed features of aggregates; moreover, markedly increased expression of Nestin, CD44, RHAMM, and CD133 in 3D-HA scaffolds were found.
  
  
  CONCLUSIONS
  the behavior of U87 in our 3D-HA model is more similar to tumor growth in vivo and a stem-like phenotype is promoted. Thus, the 3D-HA scaffold could provide a useful model for CSCs study and anti-cancer therapeutics research in vitro and may have preclinical application for the screening of drug candidates.
authors.affiliation: Center for Biomaterials and Tissue Engineering, Universitat Politécnica de Valencia, Camino de Vera s/n, 46022, Valencia, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Martínez-Ramos
authors.affiliation: Center for Biomaterials and Tissue Engineering, Universitat Politécnica de Valencia, Camino de Vera s/n, 46022, Valencia, Spain.|Networking Research Centre on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Valencia, Spain.
authors.forename: Myriam
authors.initials: M
authors.lastname: Lebourg
mesh_terms: D001254:Astrocytoma / Q000378:metabolism* / Q000473:pathology; D018914:Cells, Immobilized / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D018874:Spheroids, Cellular / Q000378:metabolism / Q000473:pathology
chemical_list: D009363:Neoplasm Proteins; D006820:Hyaluronic Acid
keywords: 3D scaffold; cancer stem cells; hyaluronic acid/hyaluronan; hydrogel; tumor model