Upregulation of endogenous ICAM-1 reduces ovarian cancer cell growth in the absence of immune cells
Autor: | Marloes L, de Groote, Hinke G, Kazemier, Christian, Huisman, Bernardina T F, van der Gun, Marijke M, Faas, Marianne G, Rots |
---|---|
Rok vydání: | 2012 |
Předmět: |
Ovarian Neoplasms
Chromatin Immunoprecipitation Reverse Transcriptase Polymerase Chain Reaction Blotting Western Antineoplastic Agents Apoptosis Flow Cytometry Intercellular Adhesion Molecule-1 Real-Time Polymerase Chain Reaction Drug Resistance Neoplasm Tumor Cells Cultured Humans Female RNA Messenger Cisplatin Cell Proliferation Transcription Factors |
Zdroj: | International journal of cancer. 134(2) |
ISSN: | 1097-0215 |
Popis: | 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. |
Databáze: | OpenAIRE |
Externí odkaz: |