MAGE-A3 is highly expressed in a cancer stem cell-like side population of bladder cancer cells

Int J Clin Exp Pathol. 2014 May 15;7(6):2934-41. eCollection 2014.

Abstract

Cancer stem cells (CSCs), which have the abilities of tumor-initiating, self-renewal and differentiation, are thought to cause post-therapeutic recurrence and the progression of cancer. However, CSCs are commonly resistant to current cancer therapies including chemotherapy and radiotherapy. In this study, we isolated cancer stem celllike side population (SP) cells from human bladder cancer cell line SW780 by a flow cytometry-based SP technique. SP cells were only about 3.6% of SW780 cells and showed higher expression of ATP-binding cassette sub-family G member 2 (ABCG2) and CD133. In vitro assay of tumor sphere growth as well as in vivo assay of xenograft transplantation confirmed the higher tumorigenicity of isolated SP cells. These data indicated that SP cells were enriched with CSCs of bladder cancer. Furthermore, we determined the expression of melanoma antigen family A, 3 (MAGEA3), one of the most studied cancer testis (CT) antigens, in these SP and main population (MP) cells derived from SW780 cells. SW780 SP cells representing CSCs of bladder cancer showed an up-regulated expression of MAGE-A3 and a positive coexpression of MAGE-A3 and CD133, indicating that MAGE-A3 was a novel CT antigen preferentially expressed in the CSCs of bladder cancer. In summary, our findings confirmed the existence of cancer stem cell-like SP cells in bladder cancer cells, and further indicated that MAGE-A3 is a novel CSC antigen and therefore may serve as an immunotherapeutic target for CSCs of bladder cancer.

Keywords: 3 (MAGE-A3); Melanoma antigen family A; bladder cancer; cancer stem cells; cancertestis; immunotherapy; side population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Neoplasm / biosynthesis*
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Separation
  • Female
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Heterografts
  • Humans
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Neoplasm Proteins / biosynthesis*
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Side-Population Cells / metabolism
  • Side-Population Cells / pathology*
  • Urinary Bladder Neoplasms / metabolism
  • Urinary Bladder Neoplasms / pathology*

Substances

  • Antigens, Neoplasm
  • MAGEA3 protein, human
  • Neoplasm Proteins