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-1 (ICAM-1) expression might be of interest, since the expression of ICAM-1 is lower in ovarian cancer cells compared to healthy ovarian cells and positively 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. Also in ovarian cancer, the 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 (ATFs). For a panel of ovarian cancer cells, tumor growth and cisplatin sensitivity were evaluated. Induction of ICAM-1 expression (ranging from 2- 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 re-expression by ATFs represents a powerful approach for functional validation of genes epigenetically silenced in cancer, like ICAM-1. © 2013 Wiley Periodicals, Inc.