Upregulation of endogenous ICAM-1 reduces ovarian cancer cell growth in the absence of immune cells

Int J Cancer. 2014 Jan 15;134(2):280-90. doi: 10.1002/ijc.28375. Epub 2013 Aug 10.


Ovarian cancer is a difficult-to-treat cancer with a 5-year survival rate of only ∼45%, due to late diagnosis and therapy resistance. In need of new therapeutic approaches, induction of intercellular adhesion molecule (ICAM)-1 expression might be of interest, since the expression of ICAM-1 is lower in ovarian cancer cells compared with healthy ovarian cells and correlated with decreased tumorigenicity. Whereas ICAM-1 expression on tumor cells is of importance for attracting immune cells, ICAM-1 might also induce tumorigenicity and chemoresistance. In ovarian cancer, such a role of ICAM-1 is unclear. Here, we investigated whether ICAM-1 has a cell-biological role by bidirectional modulation of ICAM-1 expression using ICAM-targeting artificial transcription factors. For a panel of ovarian cancer cells, tumor growth and cisplatin sensitivity were evaluated. Induction of ICAM-1 expression (ranging from 3- to 228-fold on mRNA level and 1.7- to 108-fold on protein level) resulted in indications of decreased ovarian cancer cell growth and reduced cisplatin sensitivity. Repression ranged from 48 to 94% on mRNA level and 47 to 91% on protein level. This study shows that, next to its established immunogenic role, ICAM-1 affects cell biological behavior of ovarian cancer cells and, importantly, that reexpression by artificial transcription factors represents a powerful approach for functional validation of genes epigenetically silenced in cancer, such as ICAM-1.

Keywords: artificial transcription factor; cisplatin; epigenetics; tumor suppressor gene; zinc finger.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Blotting, Western
  • Cell Proliferation / drug effects
  • Chromatin Immunoprecipitation
  • Cisplatin / pharmacology*
  • Drug Resistance, Neoplasm*
  • Female
  • Flow Cytometry
  • Humans
  • Intercellular Adhesion Molecule-1 / genetics
  • Intercellular Adhesion Molecule-1 / metabolism*
  • Ovarian Neoplasms / immunology
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Ovarian Neoplasms / prevention & control*
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factors / metabolism*
  • Tumor Cells, Cultured


  • Antineoplastic Agents
  • ICAM1 protein, human
  • RNA, Messenger
  • Transcription Factors
  • Intercellular Adhesion Molecule-1
  • Cisplatin