Chitosan-alginate scaffold culture system for hepatocellular carcinoma increases malignancy and drug resistance

Matthew Leung, Forrest M. Kievit, Stephen J. Florczyk, Omid Veiseh, Jennifer Wu, James O. Park, Miqin Zhang

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

Abstract

Purpose: 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.

Original languageEnglish (US)
Pages (from-to)1939-1948
Number of pages10
JournalPharmaceutical Research
Volume27
Issue number9
DOIs
StatePublished - Sep 2010
Externally publishedYes

Keywords

  • chitosan
  • drug resistance
  • hepatocellular carcinoma in vitro model
  • scaffolds
  • tumor microenvironment

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

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