Abstract:
: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 than 90% of head and neck cancers are squamous cell carcinomas (SCCHN). Approximately half of the patients afflicted die within 5 years of diagnosis and survival rates for cancer of the upper aero-digestive tract have not changed in 25 years. The opioid growth factor (OGF), ¿Met5-enkephalin, inhibits the growth of SCCHN in vitro and in vivo, and acts in a receptor-mediated fashion. Receptor binding assays using CAL-27 human SCCHN cells in culture and ¿3H-¿Met5-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 (Kd) of 5.0+/-0.9 nM and maximal binding capacity (Bmax) of 47.5+/-1.7 fmol/mg protein. Subcellular fractionation studies determined that the optimal binding occurred with the nuclear fraction. Competition experiments demonstrated that cold ¿Met5-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 almost 5-fold compared to the same cells grown in vitro. Binding to radiolabeled ¿Met5-enkephalin was recorded in SCCHN obtained from surgical resections. The function, pharmacological and biochemical characteristics, distribution and subcellular location of OGF binding in human SCCHN were consonant with the OGF receptor (OGFr).
journal_name
Int J Mol Medjournal_title
International journal of molecular medicineauthors
McLaughlin PJ,Levin RJ,Zagon ISdoi
10.3892/ijmm.5.2.191subject
Has Abstractpub_date
2000-02-01 00:00:00pages
191-6issue
2eissn
1107-3756issn
1791-244Xjournal_volume
5pub_type
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