title: Chitosan-alginate scaffold culture system for hepatocellular carcinoma increases malignancy and drug resistance.
abstract: OBJECTIVE
  Hepatocellular carcinoma (HCC) is a prevalent solid malignancy. Critically needed discovery of new therapeutics has been hindered by lack of an in vitro cell culture system that can effectively represent the in vivo tumor microenvironment. To address this need, a 3D in vitro HCC model was developed using a biocompatible, chitosan-alginate (CA) scaffold cultured with human HCC cell lines.
  
  
  METHODS
  The correlation between the cell function, such as secretion of growth factors and production of ECM in vitro, and the tumor growth and blood vessel recruitment in vivo was investigated.
  
  
  RESULTS
  HCC cells grown on 3D CA scaffolds demonstrated morphological characteristics and increased expression of markers of highly malignant cells. Implantation of CA scaffolds cultured with human HCC cells in mice showed accelerated tumor growth. Histology revealed marked differences in morphology and organization of newly formed blood vessels between tumors produced by different pre-cultured conditions. Resistance to doxorubicin was significantly pronounced in CA scaffold-cultured HCC cells compared to 2D or Matrigel cultured HCC cells.
  
  
  CONCLUSIONS
  This 3D model of HCC, with its ability to more closely mimic the in vivo tumor behavior, may serve as an invaluable model for study and application of novel anticancer therapeutics against HCC.
authors.affiliation: Department of Materials Science & Engineering, University of Washington, Seattle, Washington 98195, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Leung
authors.forename: Forrest M
authors.initials: FM
authors.lastname: Kievit
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Florczyk
authors.forename: Omid
authors.initials: O
authors.lastname: Veiseh
authors.forename: Jennifer
authors.initials: J
authors.lastname: Wu
authors.forename: James O
authors.initials: JO
authors.lastname: Park
authors.forename: Miqin
authors.initials: M
authors.lastname: Zhang
mesh_terms: D000464:Alginates / Q000737:chemistry*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001672:Biocompatible Materials / Q000737:chemistry; D018929:Cell Culture Techniques / Q000379:methods; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry*; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000098:blood supply / Q000188:drug therapy / Q000378:metabolism / Q000648:ultrastructure*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008855:Microscopy, Electron, Scanning; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D054457:Tissue Scaffolds / Q000737:chemistry*; D023041:Xenograft Model Antitumor Assays / Q000379:methods*
chemical_list: D000464:Alginates; D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D006603:Hexuronic Acids; D004317:Doxorubicin; D020723:Glucuronic Acid; D048271:Chitosan