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Defects in the opioid growth factor receptor in human squamous cell carcinoma of the head and neck
Patricia J McLaughlin1, Brendan C Stack, Roger J Levin
1Department of Neuroscience and Anatomy, Division of Otolaryngology, The Milton S. Hershey Medical Center, The Pennsylvania State University, Hershey, Pennsylvania 17033, USA. pxm9@psu.edu
Background:
The endogenous opioid peptide, [Met(5)]-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.
Insights
Opioid growth factor receptor (OGFr) is reduced in head and neck cancer, with lower protein but normal gene levels. This OGFr defect may drive tumor progression and could be a diagnostic marker.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- The opioid growth factor (OGF) acts as an inhibitory growth factor for epithelial cells via its receptor (OGFr).
- Squamous cell carcinoma of the head and neck (SCCHN) is a significant malignancy with complex regulatory pathways.
- Understanding OGFr's role in SCCHN is crucial for developing targeted therapies.
Purpose of the Study:
- To compare protein and gene expression of OGFr in SCCHN tissues versus normal epithelium.
- To investigate the potential of OGFr as a biomarker for SCCHN.
- To explore the implications of OGFr dysregulation in SCCHN pathogenesis.
Main Methods:
- Analysis of surgical specimens from SCCHN patients and controls.
- Receptor binding assays to assess OGFr binding affinity and capacity.
- Quantitative Western blot and Northern blot analyses for OGFr protein and mRNA levels.
- Immunohistochemistry to determine OGFr distribution.
Main Results:
- Tumor tissues exhibited significantly reduced OGFr binding capacity (nearly ninefold lower) and protein levels (fivefold lower) compared to normal epithelium.
- OGFr mRNA levels were comparable between SCCHN tissues and normal epithelium.
- Tumor margins showed intermediate protein and binding levels, with normal mRNA levels.
Conclusions:
- OGFr is defective in SCCHN, primarily due to post-transcriptional dysregulation.
- Reduced OGFr levels and binding capacity may serve as a biomarker for SCCHN.
- Therapeutic strategies aimed at restoring OGFr function could offer a novel approach to inhibit SCCHN progression.
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