Fucosylation is a common glycosylation type in pancreatic cancer stem cell-like phenotypes

World J Gastroenterol. 2015 Apr 7;21(13):3876-87. doi: 10.3748/wjg.v21.i13.3876.

Abstract

Aim: To evaluate/isolate cancer stem cells (CSCs) from tissue or cell lines according to various definitions and cell surface markers.

Methods: Lectin microarray analysis was conducted on CSC-like fractions of the human pancreatic cancer cell line Panc1 by establishing anti-cancer drug-resistant cells. Changes in glycan structure of CSC-like cells were also investigated in sphere-forming cells as well as in CSC fractions obtained from overexpression of CD24 and CD44.

Results: Several types of fucosylation were increased under these conditions, and the expression of fucosylation regulatory genes such as fucosyltransferases, GDP-fucose synthetic enzymes, and GDP-fucose transporters were dramatically enhanced in CSC-like cells. These changes were significant in gemcitabine-resistant cells and sphere cells of a human pancreatic cancer cell line, Panc1. However, downregulation of cellular fucosylation by knockdown of the GDP-fucose transporter did not alter gemcitabine resistance, indicating that increased cellular fucosylation is a result of CSC-like transformation.

Conclusion: Fucosylation might be a biomarker of CSC-like cells in pancreatic cancer.

Keywords: Anti-cancer drug resistance; Cancer stem cells; Fucosylation; Glycosylation; Pancreatic cancer; Sphere formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimetabolites, Antineoplastic / pharmacology
  • CD24 Antigen / genetics
  • CD24 Antigen / metabolism
  • Cell Line, Tumor
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Resistance, Neoplasm
  • Fucose / metabolism*
  • Fucosyltransferases / genetics
  • Fucosyltransferases / metabolism
  • Galactoside 2-alpha-L-fucosyltransferase
  • Gemcitabine
  • Glycosylation
  • Humans
  • Hyaluronan Receptors / genetics
  • Hyaluronan Receptors / metabolism
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / metabolism*
  • Pancreatic Neoplasms / drug therapy
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism*
  • RNA Interference
  • Spheroids, Cellular
  • Transfection

Substances

  • Antimetabolites, Antineoplastic
  • CD24 Antigen
  • CD24 protein, human
  • CD44 protein, human
  • Hyaluronan Receptors
  • Deoxycytidine
  • Fucose
  • Fucosyltransferases
  • Gemcitabine