Abstract

Human neuroblastoma is one of the most common solid tumors in infants and children and represents about 10% of all childhood cancers. Nearly 70% of the patients present with disseminated disease and the long-term prognosis remains poor for this group despite advances in diagnosis and therapy. In this study, we discovered that an endogenous opioid peptide, [Met5]-enkephalin, inhibited the growth of human neuroblastoma SK-N-SH in vitro; in view of this pentapeptide's action it has been termed opioid growth factor (OGF). OGF was found to be constitutively expressed and tonically capable of suppressing cell replication, and its effects were opioid receptor mediated. Growth inhibition was dose-related, reversible, not cytotoxic, and independent of serum. Immunocytochemical studies detected both OGF and its related receptor, zeta, in the cytoplasm of log-phase cells. Pharmacological binding assays revealed specific and saturable binding with a one-site model of kinetics; this high-affinity opioid receptor was identified as zeta. These data suggest that a native opioid peptide, OGF, interacts with a novel opioid receptor, zeta, to arrest the growth of human neuroblastoma.