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Sigma and opioid receptors in human brain tumors
G E Thomas1, M Szücs, J Y Mamone
1Department of Biochemistry, St. Louis University School of Medicine, Missouri 63104.
Abstract:
Human brain tumors (obtained as surgical specimens) and nude mouse-borne human neuroblastomas and gliomas were analyzed for sigma and opioid receptor content. Sigma binding was assessed using [3H]1,3-di-o-tolylguanidine (DTG), whereas opoid receptor subtypes were measured with tritiated forms of the following: mu, [D-ala2,mePhe4,gly-ol5]enkephalin (DAMGE); kappa, ethylketocyclazocine (EKC) or U69,593; delta, [D-pen2,D-pen5]enkephalin (DPDPE) or [D-ala2,D-leu5]enkephalin (DADLE) with mu suppressor present. Binding parameters were estimated by homologous displacement assays followed by analysis using the LIGAND program. Sigma binding was detected in 15 of 16 tumors examined with very high levels (pmol/mg protein) found in a brain metastasis from an adenocarcinoma of lung and a human neuroblastoma (SK-N-MC) passaged in nude mice. kappa opioid receptor binding was detected in 4 of 4 glioblastoma multiforme specimens and 2 of 2 human astrocytoma cell lines tested but not in the other brain tumors analyzed.
Insights
Researchers investigated sigma and opioid receptors in human brain tumors and neuroblastomas. Sigma receptors were found in most tumors, with particularly high levels in lung adenocarcinoma metastasis and neuroblastoma.
Area of Science:
- Neuroscience
- Oncology
- Pharmacology
Background:
- Sigma and opioid receptors are implicated in various physiological processes.
- Their role in human brain tumors remains incompletely understood.
- Understanding receptor expression can inform targeted therapies.
Purpose of the Study:
- To quantify sigma and opioid receptor expression in human brain tumors.
- To assess receptor content in both primary tumors and xenografts.
- To identify potential differences in receptor expression across tumor types.
Main Methods:
- Analysis of surgical human brain tumor specimens and nude mouse xenografts.
- Radioligand binding assays using [3H]1,3-di-o-tolylguanidine (DTG) for sigma receptors.
- Measurement of mu, kappa, and delta opioid receptor subtypes using specific radiolabeled ligands and competitive binding assays.
- Data analysis using the LIGAND program for binding parameter estimation.
Main Results:
- Sigma receptor binding was detected in 15 out of 16 human brain tumors analyzed.
- Very high sigma receptor levels were observed in a lung adenocarcinoma metastasis and a human neuroblastoma xenograft (SK-N-MC).
- Kappa opioid receptor binding was present in glioblastoma multiforme specimens and astrocytoma cell lines, but not in other analyzed brain tumors.
Conclusions:
- Human brain tumors frequently express sigma receptors, with notable exceptions in specific metastatic and neuroblastic tumors.
- Kappa opioid receptor expression is restricted to certain glial tumors like glioblastoma and astrocytoma.
- These findings suggest differential expression patterns of sigma and opioid receptors in human brain tumors, potentially offering therapeutic targets.