Defects in the opioid growth factor receptor in human squamous cell carcinoma of the head and neck

BACKGROUND. The endogenous opioid peptide, [Met⁵]-enkephalin, termed opioid growth factor (OGF), interacts with its receptor (OGFr) to play a role as a constitutively expressed inhibitory growth factor in the proliferation of epithelial cells. This study compared protein and gene expression of OGFr in surgical specimens of human squamous cell carcinoma of the head and neck (SCCHN) with normal epithelium. METHODS. Tissues from 64 patients with SCCHN and from 49 patients undergoing uvulapalatoplasty or tonsillectomy were utilized. Binding affinity and capacity were assessed by receptor binding assays and the levels of OGFr protein were determined by quantitative Western blot analysis. Immunohistochemistry assessed the presence and distribution of OGFr. Levels of OGFr mRNA were quantitated by Northern blot analysis. Protein and gene expressions of OGFr also were evaluated in the margins of SCCHN. RESULTS. Binding analyses indicated nearly ninefold fewer OGFr binding sites in tumor tissue in comparison with normal samples. The OGFr protein levels were reduced fivefold in tumor tissues relative to normal epithelium. Values of OGFr mRNA were comparable in tumors and normal epithelium. Tumor margins had intermediate levels of protein and binding, but OGFr mRNA values were similar to those of normal specimens. CONCLUSIONS. These data demonstrate that OGFr is defective in SCCHN and that translation/posttranslation of OGFr protein, but not transcriptional levels of the OGFr gene, is involved. In addition, the attenuated levels of OGFr binding capacity may serve as a marker for SCCHN. These subnormal levels of OGFr may be responsible in part for tumor progression, diminishing the interaction of OGF with OGFr that aids in stabilizing cell replication by an inhibitory mechanism. Gene therapy to reinstate OGFr and/or function could provide a useful treatment for inhibiting tumor progression.