Epithelial Ovarian Cancer (EOC) is the leading cause of death from gynaecological malignancy in the developed world. Epidemiological evidence indicates number of lifetime ovulations as being a major risk factor for the development of the disease. As ovulation is an inflammatory process, it is thought that repetitive inflammation-associated damage to the ovarian surface epithelium (OSE) leads to oncogenic events within these cells. Previous studies have demonstrated that healthy OSE cells express 11βHSD1 in response to inflammatory cytokine stimulation, leading to regeneration of cortisol from cortisone, and this system is suggested to provide anti-inflammatory steroid cover to protect OSE from inflammatory damage. Moreover, a feed-forward mechanism exists in OSE, whereby cortisol, in the presence of inflammatory cytokines, augments the inflammation-driven increase in 11βHSD1 expression. The aim of the current study was therefore to investigate whether or not such an anti-inflammatory response was dysregulated in primary EOC cells.
Primary cultures of OSE and EOC were established from solid tumour and ascites obtained with informed consent and with Local Research Ethics Committee approval. Cells were treated with Interleukin 1-alpha at 0.5 ng/ml (IL1), in the presence and absence of 1μM cortisol (F) for 48 hours. RNA extraction was performed and mRNA expression of 11βHSD 1 and 2 isotypes assessed by quantitative RT-PCR.
In cultures of human OSE cells (n=4), the mean fold rise in 11βHSD1 was significantly greater than in the EOC samples (n=11) when treated with IL1 (27.2 vs 4.0, P<0.05) and with IL1 and F (63.9 vs 11.1, P<0.05). Levels of 11βHSD2 were not significantly altered by any of the treatments in cultures of EOC or OSE.
These data provide evidence that EOC cells have impaired ability to mount an anti-inflammatory response. This may be an important feature of disease development.