The process of ovulation is believed to contribute to the majority of ovarian cancers that derive from the ovarian surface epithelium (OSE). The OSE is known to be important for successful ovulation and more recently was shown to be sensitive to inflammatory cytokines such as interleukin-1alpha (IL-1alpha; Human Reproduction: 17:2300-2306).
Normal OSE cells were obtained, with informed consent and local ethical committee approval, from premenopausal women during laparotomy for benign gynaecological conditions. Primary OSE cell cultures from three separate patients were compared directly with cell lines derived from poorly differentiated (SKOV-3, PEO-4) and well differentiated (PEO-14) ovarian adenocarcinoma. Cells were incubated with 0.25, 0.5 and 1 nanograms per mililitre IL-1alpha for 48 hours, and RNA isolated and examined by RT-PCR using agarose gel electrphoresis or real-time PCR analysis.
Relative to SKOV-3 and PEO-4 cells, HOSE cells and PEO-14 cells consistently expressed a low level of 11 betaHSD (hydroxysteroid dehydrogenase) type 2 and high level of 11 betaHSD type 1, Cox (cyclooxygenase) 2 and IL-1 receptor mRNA. When treated with IL-1alpha, the levels of 11 betaHSD type 1 and Cox 2 mRNAs markedly increased (>20 fold, P<0.01) in HOSE cells with little effect observed in cancer cell lines. The level of 11 betaHSD type 2 mRNA level was unaffected by IL-1alpha in HOSE and SKOV-3 cells, however, an increase (>2 fold, P<0.05) of 11 betaHSD type 2 mRNA level ocurred in PEO-4 and PEO-14 cells in response to IL-1alpha.
Our results indicate that cell lines derived from ovarian cancers have lost the ability to respond normally to inflammatory cytokines such as IL-1alpha; this is most noticeable in cells derived from poorly differentiated carcinomas that demonstrate a reduced level of 11 betaHSD type 1, Cox 2 and IL-1 receptor and increased level of 11 betaHSD type 2.
This research was supported by The Medical Research Council Programme Grant number 0000066 and The European Commission EU Contract EUK1-CT-2002-00128 (EURISKED).
22 - 24 Mar 2004
British Endocrine Societies