Researchers at The Pennsylvania State University College of Medicine, Hershey, Pennsylvania have discovered that the presence and integrity of the opioid growth factor receptor (OGFr), which mediates the inhibitory action of opioid growth factor (OGF) on cell proliferation, is a key to understanding the progression and treatment of human ovarian cancer. Transplantation of human ovarian cancer cells that were molecularly engineered to have a reduced expression of OGFr, into immunocompromised mice resulted in ovarian tumors that grew rapidly. This discovery, reported in the February 2012 issue of Experimental Biology and Medicine, provides fresh new insights into the pathogenesis and therapy of a lethal cancer that is the fifth leading cause of cancer-related mortality among women in the USA, and has a death rate that is unchanged for over 75 years.
The OGF (also-termed [Met5]-enkephalin)-OGFr axis plays a fundamental role in cancer, development, and cellular renewal by regulating cell proliferation. An important question addressed in this study relates to the requirement of this peptide-receptor system for the progression of carcinogenesis. Human ovarian cancer cell lines that were genetically modified to underexpress OGFr grew far more rapidly in tissue culture than control (empty vector/wildtype) cell lines. Moreover, the addition of OGF to cultures of these genetically modified cells did not respond to the inhibitory peptide and change cell number, indicating that the loss of OGFr interfered with the function of the OGF-OGFr axis with respect to regulating cell proliferation. Immunocompromised mice injected with ovarian cancer cells that had a reduction in OGFr displayed tumors much earlier than controls, and these tumors grew faster than controls. Putting this information together with knowledge that the pathway for OGF-OGFr regulation of cell proliferation in ovarian cancer is by way of increasing the cyclin-dependent inhibitory kinas
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Society for Experimental Biology and Medicine