Overexpression of sigma receptors in nonneural human tumors
Bem, W.T.; Thomas, G.E.; Mamone, J.Y.; Homan, S.M.; Levy, B.K.; Johnson, F.E.; Coscia, C.J.
Cancer Research 51(24): 6558-6562
1991
ISSN/ISBN: 0008-5472 PMID: 1660342 Document Number: 375724
Previously data indicated that opioid receptors occur in both neural and nonneural human tumors. However, it has recently been shown that some of of the putative opioid binding may be attributable to .sigma. sites. In this study the occurrence of .sigma. and opioid receptors in nonneural human tumors was assessed. The neoplasms included renal and colon carcionomas and a sarcoma. [3H]1,3-di-o-tolyguanidine was used to assay .sigma. receptors by homologous competition binding assays, which when analyzed provided dissociation constant and receptor density values. Opioid binding was measured with [3H]-(-)-ethylketocyclazocine, a ligand which interacts with .mu., .delta., and .kappa. subtypes. Fresh surgical specimens were obtained from 9 human neoplasms, selected for their large size, and compared with nonmalignant tissues. All 9 tumors contained .sigma. sites, and dissociation constant values were within the range of 27-83 nM. Occassionally, two-site fit the data better than one-site binding, suggesting the presence of multiple .sigma. sites. Opioid binding was not detected. Intratumoral variability was evaluated by sampling several locations on the periphery of the mass and one in the center. Each of the samples was bisected, with a portion reserved for histological examination to correlate morphological features with receptor data. Changes in .sigma. binding were not associated with the extent of fibrosis, viability, or necrosis. Receptor density values displayed moderate intra- and intertumoral variation (coefficients of variation, 8-39 and 27-49%, respectively). More important, .sigma. binding in tumros was found to be >EQ 2-fold higher than that of control nonmalignant tissue.