Regulation of human head and neck squamous cell carcinoma growth in tissueculture by opioid growth factor

Squamous cell carcinoma of the head and neck (SCCHN) is the sixth most comm on malignancy worldwide. Approximately half of the patients afflicted die w ithin 5 years of diagnosis, and surviving patients may be left with severe esthetic and functional compromise. In this study, we discovered that an en dogenous opioid peptide, [Met(5)]-enkephalin, inhibited the growth of human SCCHN in vitro; in view of this pentapeptide's action it has been termed o pioid growth factor (OGF). OOF was found to be a constitutively expressed, receptor-mediated growth inhibitory agent that appears to be autocrine prod uced and secreted. Growth regulation was dose-related, reversible, cytostat ic, and independent of serum. All 6 human SCCHN cell lines examined exhibit ed growth modulation by OGF. Blockade of peptide-receptor interaction by op ioid antagonists (naltrexone), or addition of antibody to OGF, resulted in substantial increases in cell number compared to control levels, showing th e tonic nature of OGF-zeta activity. Immunocytochemical studies detected bo th OGF and its related receptor, 5, in these cells, correlating with earlie r findings of peptide and receptor in specimens of SCCHN obtained at surger y. These data suggest that a native opioid peptide, OGF, interacts with a n ovel opioid receptor, zeta, to tonically arrest the growth of human SCCHN.