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Expression of somatostatin receptor subtypes in human brain tumors
1Laboratory of Experimental Neuroendocrinology, Hôpital Nord University of Marseille, France.
Abstract:
Expression of mRNA for the 5 somatostatin receptors (sst1-5) was characterized by Northern blot and RT-PCR analysis in 20 meningioma and 9 glioma samples. sst1 mRNA was detectable by Northern blots of poly-A+ RNA in meningiomas but not gliomas. In contrast, sst2 mRNA was readily detected by Northern blots of total RNA as a major 2.3 kb transcript and 2 minor 4.3 kb and 8 kb transcripts in all meningiomas and 6 out of 9 gliomas. Quantitation of the 2.3 kb sst2 mRNA showed that 15 out of 20 tumors expressed 1.3- to 33-fold higher levels than control normal human brain. Mean sst2 mRNA for the 20 meningioma samples was 978% that of normal brain. Three gliomas showed 7- to 14-fold higher sst2 mRNA than normal brain whereas the remaining samples displayed very low or undetectable levels. Immunocytochemistry of meningioma and glioma samples, with a sst2-specific antibody revealed immunoreactivity in tumor cells and peritumoral tissue, with prominent expression in blood vessels. mRNA for sst3,4,5 could not be detected by Northern blots in any of the tumors. RT-PCR analysis of meningiomas and gliomas revealed the following percent of tumors positive for a given sst mRNA: sst1 (86%), sst2 (100%), sst3 (60%), sst4 (58%), and sst5 (67%); 85% of tumors expressed 3 of the 5 subtypes. No correlation was found between the pattern of expression of sst mRNA and tumor type, location, and histology for either the meningiomas or gliomas. Our results show that meningiomas and gliomas are all positive for at least one sst subtype, the majority expressing multiple subtypes. sst2 is the most abundant isoform with a rich expression in both tumor and peritumoral tissue especially blood vessels.
Insights
Meningiomas and gliomas commonly express somatostatin receptors (sst), particularly sst2, in tumor cells and blood vessels. Most brain tumors show multiple sst subtypes, indicating potential therapeutic targets.
Area of Science:
- Neuro-oncology
- Molecular Biology
- Receptor Pharmacology
Background:
- Meningiomas and gliomas are primary brain tumors with varying treatment outcomes.
- Somatostatin receptors (sst) are implicated in cell growth and signaling pathways.
- Understanding sst expression in brain tumors may reveal therapeutic targets.
Purpose of the Study:
- To characterize the expression of somatostatin receptor subtypes (sst1-5) mRNA in human meningioma and glioma samples.
- To investigate the abundance and distribution of sst2 mRNA and protein in these tumors.
- To explore potential correlations between sst expression patterns and tumor characteristics.
Main Methods:
- Northern blot and reverse transcription-polymerase chain reaction (RT-PCR) were used to analyze sst mRNA expression.
- Immunocytochemistry with an sst2-specific antibody was performed to assess protein localization.
- Quantification of sst2 mRNA levels was compared to normal human brain tissue.
Main Results:
- All meningioma and glioma samples expressed at least one sst subtype, with most expressing multiple.
- sst2 mRNA was the most abundant isoform, detected in all meningiomas and most gliomas, often at higher levels than normal brain.
- sst2 immunoreactivity was observed in tumor cells, peritumoral tissue, and prominently in blood vessels.
Conclusions:
- Meningiomas and gliomas exhibit widespread expression of somatostatin receptors, with sst2 being the predominant subtype.
- The significant expression of sst2, especially in tumor vasculature, suggests its potential as a therapeutic target for these brain tumors.
- No correlation was found between sst mRNA expression patterns and tumor type, location, or histology.