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

de Groote, M. L., Kazemier, H. G., Huisman, C., van der Gun, B. T. F., Faas, M. M. & Rots, M. G., 15-Jan-2014, In : International Journal of Cancer. 134, 2, p. 280-290 11 p.

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  • Upregulation of endogenous ICAM-1 reduces ovarian cancer cell growth

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DOI

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
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

ID: 5987101