alpha-endorphin and Neoplasms

The role of enkephalins, endorphins and other neuropeptides produced by the nervous system in the alteration of immune responsiveness is generally unknown. The present studies were undertaken to investigate the role of these neuropeptides in the modulation of cytotoxicity induced by LPS activated macrophages obtained from normal donors as well as breast cancer and Hodgkins disease patients. When the macrophages from normal donors were pretreated with these neuropeptides for 1 hr prior to co-culturing with target cells, macrophage mediated cytotoxicity was enhanced with 10(-6) M and 10(-8) M of [met]-enkephalin, 10(-6) M of [leu]-enkephalin and 10(-6) M and 10(-12) M of alpha-endorphin. However, when the macrophages were co-cultured with target cells in the presence of the neuropeptides, it was observed that 10(-6) M and 10(-12) M of alpha-endorphin enhanced cytotoxicity whereas no enhancement in cytotoxicity was observed when [met]-enkephalin or [leu]-enkephalin were added to the cultures. In fact, it appears that 10(-10) M of [met]-enkephalin and 10(-12) M of [leu]-enkephalin actually suppressed macrophage mediated cytotoxicity. When the opioid antagonist Naloxone was incubated with the neuropeptides in the presence of the macrophages the enhancement of macrophage killing produced by [met]-enkephalin, [leu]-enkephalin or alpha-endorphin was suppressed. When the breast cancer patients' macrophages were pretreated with these neuropeptides, enhancement in cytotoxicity was observed at 10(-10) M of [met]-enkephalin, and [leu]-enkephalin and at 10(-8) M and 10(-12) M of alpha-endorphin.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: alpha-Endorphin; Breast Neoplasms; Cell Line; Cytotoxicity, Immunologic; Endorphins; Enkephalin, Leucine; Enkephalin, Methionine; Hodgkin Disease; Humans; Macrophages; Naloxone; Neoplasms; Neuropeptides

We looked for opioid peptides and their precursors in 108 tumors of both neuroendocrine and nonneuroendocrine origin, using a monoclonal "pan-opioid" antibody, 3-E7, which recognizes the tetrapeptide Tyr-Gly-Gly-Phe (the sequence responsible for pharmacologic activity in all known opioid peptides), in conjunction with polyclonal antibodies directed against representative peptides of each of the three precursors (alpha-endorphin, [met]enkephalin-Arg-Gly-Leu, and dynorphin B). Using the avidin-biotin immunoperoxidase technique, we observed consistent cytoplasmic immunoreactivity (at least focally) in all of 15 adrenal pheochromocytomas, all of 6 thyroid medullary carcinomas, and all of 5 pituitary adenomas. Opioid staining was also observed in parathyroid adenomas (8 of 9), pancreatic islet-cell tumors (7 of 10), carcinoid tumors from various sites (18 of 26), and paragangliomas (1 of 2). There was no immunoreactivity in pulmonary small-cell carcinomas, Merkel-cell tumors of skin, neuroblastomas, or any of the non-neuroendocrine tumors examined. The expression of alpha-endorphin, [met]enkephalin-Arg-Gly-Leu, and dynorphin B varied from tumor to tumor; however, positive staining with the "pan-opioid" antibody was found in each tumor containing at least one of the three precursors. Opioid peptide immunoreactivity was also detected in non-neoplastic cells of the adrenal medulla, pancreatic islets, pituitary, intestinal and bronchial mucosa, and intestinal myenteric plexuses. We conclude that opioid expression within tumors is most likely due to enhanced expression of a normal cell product and that opioid peptides are useful markers of neuroendocrine differentiation in many tumors.

Topics: alpha-Endorphin; Antibodies, Monoclonal; Biomarkers, Tumor; Dynorphins; Endocrine System Diseases; Endorphins; Humans; Immunoenzyme Techniques; Neoplasms; Neurosecretory Systems; Peptide Fragments