Expression of Opioid Growth Factor (OGF)-OGF Receptor (OGFr) Axis in Human Nonmedullary Thyroid Cancer

Background: Although thyroid cancers are readily treatable with surgery and radioactive iodine, there are problems in managing recurring, as well as locally advanced, thyroid cancer. The opioid growth factor (OGF) and its receptor, OGF receptor (OGFr), form a tonically active, autocrine-paracrine loop that serves to inhibit cell proliferation in a wide variety of normal and abnormal cells and tissues. In the present study we examined the presence and distribution of OGF and OGFr in nonmedullary thyroid cancer, including papillary, follicular, and anaplastic, as well as thyroid tissue from patients with nonmalignant disease. Methods: Patient samples of thyroid cancers and goiter were collected at the time of resection and processed for immunohistochemistry of OGF and OGFr, as well as pharmacological binding assays for OGFr. Results: Both peptide and receptor were detected in the cytoplasm and nucleus of all nonmedullary thyroid cancers, as well as in goiter. Specific and saturable binding of OGFr was found in all thyroid samples. Conclusions: The finding that a potent negative growth regulator and its receptor are present in nonmedullary thyroid cancers and thyroid tissues from patients with nonmalignant disease lead us to suggest that the OGF OGFr axis serves as a regulator of cell proliferation in these tissues. Moreover, modulation of this biological system may be used to treat progression of nonmedullary thyroid neoplasias.