The opioid growth factor receptor in human head and neck squamous cell carcinoma

Carcinoma of the head and neck is the sixth leading cause of cancer in the world, and the third most common neoplasia in developing countries. More th an 90% of head and neck cancers are squamous cell carcinomas (SCCHN). Appro ximately half of the patients afflicted die within 5 years of diagnosis and survival rates for cancer of the upper aerodigestive tract have not change d in 25 years. The opioid growth factor (OGF), [Met(5)]-enkephalin, inhibit s the growth of SCCHN ill vitro and in vivo, and acts in a receptor-mediate d fashion. Receptor binding assays using CAL-27 human SCCHN cells in cultur e and [H-3]-[Met(5)]-enkephalin were employed to identify and characterize the receptor responsible for the growth-regulatory effects of OGF. Specific and saturable binding was recorded, and Scatchard analysis showed that the data were consistent for a single binding site with a binding affinity (K- d) of 5.0+/-0.9 nM and maximal binding capacity (B-max) of 47.5+/-1.7 fmol/ mg protein. Subcellular fractionation studies determined that the optimal b inding occurred with the nuclear fraction. Competition experiments demonstr ated that cold [Met(5)]-enkephalin was at least 7-fold greater than ligands selective for classical opioid receptors. Binding was detected in 4 other SCCHN cell lines. Receptor number in xenografts of CAL-27 was decreased alm ost 5-fold compared to the same cells grown in vitro. Binding to radio-labe led [Met(5)]-enkephalin was recorded in SCCHN obtained from surgical resect ions. The function, pharmacological and biochemical characteristics, distri bution and subcellular location of OGF binding in human SCCHN were consonan t with the OGF receptor (OGFr).