Alpha-fetoprotein producing cells act as cancer progenitor cells in human cholangiocarcinoma

Cancer Lett. 2010 Aug 1;294(1):25-34. doi: 10.1016/j.canlet.2010.01.019. Epub 2010 Feb 10.

Abstract

We aimed to demonstrate that alpha-fetoprotein (AFP)-producing cells in cholangiocarcinomas possessed cancer stem cell (CSC)-like properties. AFP enhancer/promoter-driven EGFP gene was transfected into human cholangiocarcinoma cell lines. One cell line, RBE, expressed both AFP and EGFP. Clonal analyses revealed that one EGFP-positive cell generated both EGFP-positive and EGFP-negative cell fractions. However, one EGFP-negative cell never produced EGFP-positive cells. The EGFP-positive cells had a greater tumorigenic potential. Only the EGFP-positive cells expressed Notch1. AFP and Notch1 expression was observed in clinical intrahepatic cholangiocarcinomas. The AFP-producing cells were suggested to be CSCs. The Notch pathway might play an important role in maintaining the CSC characteristics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Animals
  • Bile Duct Neoplasms / metabolism*
  • Bile Duct Neoplasms / pathology
  • Bile Ducts, Intrahepatic
  • Biomarkers / metabolism
  • Cell Division
  • Cell Line, Tumor
  • Cholangiocarcinoma / metabolism*
  • Cholangiocarcinoma / pathology
  • Enhancer Elements, Genetic
  • Female
  • Genes, Reporter
  • Genetic Vectors
  • Green Fluorescent Proteins / genetics
  • Humans
  • Male
  • Mice
  • Mice, Inbred NOD
  • Middle Aged
  • Neoplastic Stem Cells / metabolism*
  • Plasmids
  • Promoter Regions, Genetic
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transfection
  • Transplantation, Heterologous
  • alpha-Fetoproteins / biosynthesis
  • alpha-Fetoproteins / genetics*

Substances

  • Biomarkers
  • alpha-Fetoproteins
  • Green Fluorescent Proteins