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

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.

• Authors: Motoko Izumiya, Ayano Kabashima, Hajime Higuchi, Toru Igarashi, Gen Sakai, Hideko Iizuka, Shoko Nakamura, Masayuki Adachi, Yasuo Hamamoto, Shinsuke Funakoshi, Hiromasa Takaishi, Toshifumi Hibi
• Journal: Anticancer research (Anticancer Res) Vol. 32 Issue 9 Pg. 3847-53 (Sep 2012) ISSN: 1791-7530 [Electronic] Greece
• PMID: 22993328 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antimetabolites, Antineoplastic
• Homeodomain Proteins
• NANOG protein, human
• Nanog Homeobox Protein
• Octamer Transcription Factor-3
• POU5F1 protein, human
• Transforming Growth Factor beta
• Fluorouracil

Topics

• Antimetabolites, Antineoplastic (pharmacology)
• Apoptosis (drug effects, physiology)
• Cell Growth Processes (drug effects, physiology)
• Cell Line, Tumor
• Drug Resistance, Neoplasm
• Epithelial-Mesenchymal Transition (drug effects, genetics)
• Fluorouracil (pharmacology)
• Homeodomain Proteins (biosynthesis, genetics)
• Humans
• Nanog Homeobox Protein
• Neoplastic Stem Cells (pathology)
• Octamer Transcription Factor-3 (biosynthesis, genetics)
• Pancreatic Neoplasms (drug therapy, genetics, pathology)
• Transforming Growth Factor beta (pharmacology)