Expression of the opioid growth factor–opioid growth factor receptor axis in human ovarian cancer

Abstract

ObjectiveThe opioid growth factor (OGF) and its receptor (OGFr), serve as inhibitory axis regulating cell proliferation in normal cells and cancer. We investigated the presence and relative expression of OGF and OGFr in normal human ovarian surface epithelial (HOSE) cells, benign ovarian cysts, and ovarian cancers. MethodsSurgical samples of 16 patients with ovarian cancer and 27 patients with ovarian benign cysts were obtained intraoperatively. HOSE were collected by scraping the surface of normal ovaries of 10 post menopausal women undergoing hysterectomy and oophorectomy. Semiquantitative immunohistochemistry was used to assess the presence, distribution, and levels of OGF and OGFr. Receptor binding assays measured binding capacity and affinity of OGFr for radiolabeled OGF. ResultsOGF and OGFr were present in HOSE cells, ovarian cysts, and ovarian cancers. Compared to HOSE cells, OGF and OGFr protein levels were reduced 29% and 34% (p<0.001), respectively, in ovarian cysts, and decreased 58% and 48% (p<0.001), respectively, in ovarian cancers. Binding assays revealed 5.4 fold fewer OGFr binding sites in cancers than cysts (p<0.05). Levels of OGF and OGFr were comparable in primary, metastatic, or recurrent ovarian cancers. ConclusionWe have shown that a native opioid pathway, the OGF–OGFr axis, is present in human ovarian cancer. Importantly, the expression of OGF and OGFr is diminished in human ovarian cancer. As OGF and OGFr normally function in maintaining cell proliferation, therapy to harness OGF/OGFr function could provide a useful biologic-based treatment for human ovarian cancer.