Chemoresistance is associated with cancer stem cell-like properties and epithelial-to-mesenchymal transition in pancreatic cancer cells

Motoko Izumiya, Ayano Kabashima, Hajime Higuchi, Toru Igarashi, Gen Sakai, Hideko Iizuka, Shoko Nakamura, Masayuki Adachi, Yasuo Hamamoto, Shinsuke Funakoshi, Hiromasa Takaishi, Toshifumi Hibi

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

Background: The aim of this study was to evaluate whether apoptosis-resistant cancer cells have cancer stem cell (CSC)-like properties. Materials and Methods: Panc-1 pancreatic cancer cells were incubated in the presence of 5- fluorouracil (5-FU) for 24 h, and further incubated without 5-FU for 28 days. To assess the capacity of self-renewal, surviving cells were planted for sphere-forming assay. Epithelial-to-mesenchymal transition (EMT) was induced with TGF-β, then mRNA expression was evaluated by real-time PCR for E-cadherin, SNAIL, and vimentin. The E-Cadherin protein levels were also examined by immunoblot analysis. The Local invasion ability was analyzed by Matrigel invasion assay. Results: The frequency of cells that were capable of initiating spheres was higher in 5-FU-pre treated cells, which also overexpressed stem cell marker genes, OCT4 and NANOG. Matrigel invasion activity of apoptosis-resistant Panc-1 cells was greater than that of control Panc-1 cells. Conclusion: Apoptosis-resistant cancer cells have CSC-like properties, i.e., able to initiate sphere formation, express stem cell genes, and respond to EMT stimulation.

Original languageEnglish
Pages (from-to)3847-3853
Number of pages7
JournalAnticancer research
Volume32
Issue number9
Publication statusPublished - 2012 Sep 1

Keywords

  • 5-Fluorouracil
  • Apoptosis
  • Cancer stem cells
  • Chemoresistance
  • EMT
  • Panc-1 cells
  • Pancreatic cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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