This repair is facilitated by an increased local production the antiinflammatory steroid cortisol via up-regulation of 11ß-hydroxysteroid dehydrogenase type 1. We hypothesised that the OSE express SLITs and ROBOs and that cortisol could temporarily reduce the expression of these tumour suppressor genes to facilitate survival, proliferation and migration of these cells during the repair process. If this was the case this pathway might have a role in ovarian cancer progression and if it remains active in malignant OSE cells it may offer therapeutic strategies to manipulate these genes. We therefore investigated the expression, localisation and regulation of the SLIT/ROBO pathway in the OSE. We also examined whether the SLITs and ROBOs were aberrantly expressed and hormonally regulated in ovarian cancer cells. Furthermore we analysed the functional significance of a perturbed SLIT/ROBO pathway in ovarian cancer cells. As each of the SLITs is able to interact with each of the ROBOs, with the possible exception of ROBO4, it is likely that the SLIT/ROBO interaction is occurring in the OSE. This is not surprising as these molecules are expressed in other ovarian cells including the granulosa lutein, theca lutein and luteal fibroblasts cells of the adult corpus luteum and the pre-granulosa cells and oocytes of primordial follicles within the developing fetal ovary. The normal ovary is therefore a site of the physiological autocrine or paracrine actions of the SLIT/ROBO system.. After ovulation there is an increase in the local production of cortisol in the OSE that may act to encourage tissue repair and renewal. Over the range of physiologically relevant concentrations in OSE cells cortisol has been shown to have an anti-inflammatory action and can block interleukin-1 stimulated MMP-9 expression. In addition we have previously shown that cortisol, by negatively regulating the expression of SLITs and ROBOs, inhibits apoptosis and facilitates cell migration. This implies that after ovulation one of the effects of locally produced cortisol may be to temporarily reduce the expression of the SLIT/ROBO tumour suppressor genes to facilitate repair of the damaged OSE. In many epithelial cancers there is an associated loss of the expression of members of the SLIT/ROBO family. For example decreased expression of SLIT and ROBO transcripts has been observed in oesophageal squamous cell, hepatocellular, lung, prostate and breast carcinoma. This reduction in expression however is not universal and some cancers, such as gliomas and recurrent endometrial cancer maintain or increase the SLIT/ROBO pathway. However alterations in the expression of this pathway in malignant epithelial cells from ovarian cancer has not previously been studied. We cultured malignant epithelial cells from the ascitic fluid of patients with advanced epithelial ovarian cancer and compared SLIT/ROBO expression to that in normal OSE. We found PF-04217903 reduced expression of SLIT2, SLIT3, ROBO1, ROBO2 and ROBO4 in malignant cells.