Cancer stem-like cells enriched in Panc-1 spheres possess increased migration ability and resistance to gemcitabine

Int J Mol Sci. 2011;12(3):1595-604. doi: 10.3390/ijms12031595. Epub 2011 Mar 1.

Abstract

Pancreatic cancer is one of the most lethal malignancies with poor prognosis. Previously, we found that a subpopulation of cancer stem cells (CSCs) in the Panc-1 pancreatic cancer cell line could propagate to form spheres. Here we characterized the malignant phenotypes of the pancreatic cancer stem CD44+/CD24+ cells, which were enriched under sphere forming conditions as analyzed by flow cytometry. These cells demonstrated increased resistance to gemcitabine and increased migration ability. Moreover, these cells exhibited epithelial to mesenchymal transition characterized by a decreased level of the epithelial marker E-cadherin and an increased level of the mesenchymal marker vimentin. Notably, abnormal expression of Bmi-1, ABCG2, Cyclin D1 and p16 were found in Panc-1 CSCs. Our results suggest that targeted inhibition of CSCs represents a novel therapeutic approach to overcome chemoresistance and metastasis of pancreatic cancer.

Keywords: Bmi-1; chemoresistance; invasion; pancreatic cancer; tumorigenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters / metabolism
  • CD24 Antigen / metabolism
  • Cadherins / metabolism
  • Cell Line
  • Cell Movement / drug effects
  • Cyclin D1 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / pharmacology
  • Drug Resistance, Neoplasm
  • Epithelial-Mesenchymal Transition / drug effects
  • Humans
  • Hyaluronan Receptors / metabolism
  • Neoplasm Proteins / metabolism
  • Neoplastic Stem Cells / cytology
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / metabolism
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • Polycomb Repressive Complex 1 / metabolism
  • Vimentin / metabolism

Substances

  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • BMI1 protein, human
  • CD24 Antigen
  • Cadherins
  • Cyclin-Dependent Kinase Inhibitor p16
  • Hyaluronan Receptors
  • Neoplasm Proteins
  • Vimentin
  • Deoxycytidine
  • Cyclin D1
  • gemcitabine
  • Polycomb Repressive Complex 1