Identification of side population cells in human hepatocellular carcinoma cell lines with stepwise metastatic potentials

J Cancer Res Clin Oncol. 2008 Nov;134(11):1155-63. doi: 10.1007/s00432-008-0407-1. Epub 2008 May 10.

Abstract

Purpose: To identify the side population (SP) cells from four hepatocellular carcinoma (HCC) cell lines with stepwise metastatic potentials.

Methods: SP cells were sorted from HCCLM3, MHCC97-H, MHCC97-L and Hep3B by flow cytometry, and then analyzed by differentiation study, clonogenic assay, chemoresistance study and tumorigenicity assay in vivo. The expression of ABCG(2) in SP cells was detected by immunocytochemistry, western blotting and real-time quantitative PCR, respectively.

Results: There was significant difference in SP proportion among HCCLM3, MHCC97-H, MHCC97-L and Hep3B (28.7 +/- 1.6%, 14.5 +/- 0.6%, 4.2 +/- 0.4%, 0.9 +/- 0.1%, respectively, P < 0.01). All the SP cells showed similar characteristics of self-renewal, high clonogenicity, remarkable chemo-resistance and high expression of ABCG(2). As low as 2,000 SP cells could initiate tumors in non-obese diabetic/severe combined immunodeficiency mice successfully.

Conclusions: SP cells purified from HCC cell lines harbors cancer stem cell-like properties, and may be related to the metastatic potentials and therapeutic-resistance of HCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters / genetics
  • Carcinoma, Hepatocellular / classification*
  • Carcinoma, Hepatocellular / epidemiology
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / pathology*
  • Cell Differentiation
  • Cell Division
  • Cell Line, Tumor
  • Drug Resistance, Neoplasm
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Liver Neoplasms / classification*
  • Liver Neoplasms / epidemiology
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology*
  • Neoplasm Metastasis / pathology*
  • Neoplasm Proteins / genetics
  • Phenotype
  • Prognosis
  • Survival Rate
  • Tumor Stem Cell Assay

Substances

  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Neoplasm Proteins