Molecular characterization of CD133+ cancer stem-like cells in endometrial cancer

Int J Oncol. 2014 Mar;44(3):669-77. doi: 10.3892/ijo.2013.2230. Epub 2013 Dec 23.

Abstract

A small subset of cells with CD133 expression is thought to have increased chemoresistance and tumorigenicity, features of cancer stem cells (CSCs); the molecular mechanisms by which these properties arise remain unclear. We characterized CD133+ endometrial cancer cells based on microarray analyses of Ishikawa cells. Of the genes upregulated in CD133+ cells compared with CD133- cells, we noted several key factors involved in the aggressive behavior of cells, including ABCG2 and matrix metalloproteinase (MMP). Flow cytometric analyses identified a side-cell population (SP) with CSC features in Ishikawa cells, and they were found to be more enriched in CD133+ cells than CD133- cells. In particular, CD133+/SP cells exhibited higher proliferative and colony‑forming activity than CD133+/non-SP cells. Matrigel invasion assay revealed that CD133+ cells have enhanced invasive capacity with elevated MT1-MMP expression. siRNA‑based knockdown of MT1-MMP largely abolished the invasive capacity of CD133+ cells, but not CD133- cells due to low levels of constitutive MT1-MMP1 expression. These findings demonstrate that increased chemoresistance and tumorigenic potential of CD133+ cells are at least partly attributed to an enriched SP fraction as well as increased MMP-1 expression. These results will be of assistance in the establishment of molecular target therapy to CSCs in endometrial cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AC133 Antigen
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters / biosynthesis
  • Antigens, CD / genetics*
  • Antigens, CD / metabolism
  • Cell Line, Tumor
  • Endometrial Neoplasms / genetics*
  • Endometrial Neoplasms / pathology
  • Female
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic
  • Glycoproteins / genetics*
  • Glycoproteins / metabolism
  • Humans
  • Matrix Metalloproteinase 14 / biosynthesis
  • Microarray Analysis*
  • Neoplasm Proteins / biosynthesis
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / pathology
  • Peptides / genetics*
  • Peptides / metabolism
  • RNA, Small Interfering

Substances

  • ABCG2 protein, human
  • AC133 Antigen
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Antigens, CD
  • Glycoproteins
  • Neoplasm Proteins
  • PROM1 protein, human
  • Peptides
  • RNA, Small Interfering
  • Matrix Metalloproteinase 14