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

Marloes L. de Groote, Hinke G. Kazemier, Christian Huisman, Bernardina T. F. van der Gun, Marijke M. Faas, Marianne G. Rots*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

16 Citations (Scopus)

Abstract

Ovarian cancer is a difficult-to-treat cancer with a 5-year survival rate of only approximate to 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.

Original languageEnglish
Pages (from-to)280-290
Number of pages11
JournalInternational Journal of Cancer
Volume134
Issue number2
DOIs
Publication statusPublished - 15-Jan-2014

Keywords

  • zinc finger
  • artificial transcription factor
  • epigenetics
  • tumor suppressor gene
  • cisplatin
  • INTERCELLULAR-ADHESION MOLECULE-1
  • ARTIFICIAL TRANSCRIPTION FACTORS
  • ANTITUMOR IMMUNITY
  • BREAST-CANCER
  • GENE-TRANSFER
  • TUMOR-CELLS
  • EXPRESSION
  • CARCINOMA
  • INDUCTION
  • TUMORIGENICITY

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