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Upregulation of endogenous ICAM‐1 reduces ovarian cancer cell growth in the absence of immune cells
Author(s) -
Groote Marloes L.,
Kazemier Hinke G.,
Huisman Christian,
Gun Bernardina T.F.,
Faas Marijke M.,
Rots Marianne G.
Publication year - 2013
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.28375
Subject(s) - ovarian cancer , immune system , cancer cell , downregulation and upregulation , biology , cancer research , icam 1 , cisplatin , cancer , cell growth , medicine , immunology , cell adhesion molecule , chemotherapy , gene , biochemistry , genetics
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.