Anti-inflammatory and proliferative responses in human and ovine ovarian surface epithelial cells

Abstract

The majority of ovarian cancers (> 90%) are believed to derive from the ovarian surface epithelium (OSE); a single layer covering the entire surface of the ovary. At ovulation, the OSE cell layer undergoes an inflammatory response, involving cell death and growth, in order to overcome ovarian surface rupture. Abnormalities during these processes are believed to contribute to the development of tumours. Using primary cultures of OSE cells, we have compared anti-inflammatory and proliferative responses directly between human and ovine OSE cells to further establish the use of ovine OSE cells as a suitable model system for the study of human OSE cells. In order to compare effects of inflammatory stimulation, expression and activity of 11bhydroxysteroid dehydrogenase (11bHSD) type 1 was measured in OSE cells in response to interleukin (IL)-1a. As previously identified in human OSE cells, treatment of ovine OSE cells with IL-1a stimulated a concomitant increase of 11bHSD type 1 mRNA (31-fold; P < 0.05) and oxoreductase activity, indicating an increased production of antiinflammatory cortisol. To compare the growth of human and ovine OSE cells, OSE cell number was measured in response to treatment with gonadotropins or growth factors. In the presence of FSH, LH or human chorionic gonadotropin (hCG), ovine and human OSE cell growth was similarly stimulated > 1.2-fold (P < 0.05). In the presence of connective tissue growth factor (CTGF) and more significantly insulin growth factor I (IGF-I), human and ovine OSE cell growth was also similarly stimulated >1.2-fold (P < 0.05) and > 1.5-fold (P < 0.01), respectively. The induction of both human and ovine OSE cell growth by IGF-I or hCG was further shown to be dependent on activation of the MAP kinase/extracellular-signal-regulated kinase (ERK) pathway. Stimulation of ovine OSE cell growth by hepatocyte growth factor (HGF) was similarly shown to be ERK-dependent; however, for human OSE cells, HGF only mildly stimulated ERK phosphorylation and failed to stimulate OSE cell growth. The demonstration that human and ovine OSE cells share similarities at the level of cell signalling, gene expression and cellular growth supports the use of ovine OSE cells as a suitable model for the study of human OSE cells.

Gonadotropins and Ovarian Cancer

“…The following collection of published studies illustrates this point effectively. FSH possibly increases proliferation in the OSE and cancer cells (90, 134,136,141,143,[161][162][163][164][165], yet in other studies, no association (166) and even reduced proliferation have been observed (167,168). Some studies have reported the stimulatory effect of LH/hCG on cell growth (90, 136, 161, 163-165, 169 -173).…”

Connective tissue growth factor/CCN2 stimulates actin disassembly through Akt/protein kinase B‐mediated phosphorylation and cytoplasmic translocation of p27Kip‐1

“…Recombinant human CTGF (rhCTGF) was produced essentially as described previously (25) Briefly, rh CTGF was produced in a baculovirus expression system using Hi5 cells adapted for suspension growth and virus containing a complete human CTGF cDNA. Cells were cultured in Sf 900 II SFM (Life Technologies) supplemented with 20 g/ml gentamicin (CellGro) and 1X lipid (Life Technologies) and then scaled up for production in 3L Fernbach culture flasks (Corning, Corning, NY).…”

Ovarian Surface Epithelium in Patients with Severe Ovarian Infertility: A Potential Source of Cells Expressing Markers of Pluripotent/Multipotent Stem Cells

“…Human ovarian surface epithelium cell cultures have been set up mostly in order to study the anti-inflammatory and proliferative responses of ovarian surface epithelium cells [4, 5] and to elucidate the mechanisms of ovarian cancer formation [6–9]. During the last few years, there have also been more reports on the human ovarian surface epithelium stemness, that is, on the epithelial-mesenchymal transitions [10–12].…”