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Molecular analysis of the somatostatin receptor subtype 2 in human glioma cells
J Held-Feindt1, B Krisch, R Mentlein
1Department of Anatomy, University of Kiel, Olshausenstrasse 40 D-24098, Kiel, Germany.
Abstract:
Gliomas constantly overexpress the receptor subtype SST2 for the inhibitory peptide somatostatin. Since somatostatin or metabolically stable agonists like octreotide have an antiproliferative and antisecretory potential for the treatment of SST2-expressing tumors, we evaluated the molecular integrity of SST2 in gliomas on the DNA, mRNA and protein levels. Sequencing of about 1800 bases from the SST2 gene in nine gliomas and five control samples revealed no mutations, but polymorphisms were detected in the 5'-region irrespective of the malignancy of the sample. Gliomas and the human glioma cell line U343 expressed mRNA for the receptor splice variant SST2A with a size of about 4.2 kb. A novel antibody generated against an extracellular part of the SST2 amino acid sequence strongly reacted with an 75-kDa protein in membranes from glioma or meningioma cells and-much weaker-normal rat astrocytes. The receptor could be immunostained on the surface of intact glioma cells or (weaker) astrocytes at the light and electron microscopic level. These results show that the somatostatin receptor SST2 is non-mutated in gliomas and has similar molecular properties as in non-malignant cells.
Insights
Glioma cells overexpress the somatostatin receptor subtype 2 (SST2). This study found SST2 is non-mutated in gliomas, showing similar molecular properties to non-malignant cells, suggesting therapeutic potential.
Area of Science:
- Neuroscience
- Oncology
- Molecular Biology
Background:
- Gliomas frequently overexpress the somatostatin receptor subtype 2 (SST2).
- Somatostatin analogs like octreotide show antiproliferative potential for SST2-expressing tumors.
Purpose of the Study:
- To evaluate the molecular integrity of the SST2 receptor in gliomas at DNA, mRNA, and protein levels.
Main Methods:
- DNA sequencing of the SST2 gene in glioma and control samples.
- Analysis of SST2 mRNA expression using RT-PCR.
- Immunohistochemical and immunoelectron microscopic analysis of SST2 protein expression using a novel antibody.
Main Results:
- No mutations were detected in the SST2 gene of gliomas; polymorphisms were found in the 5'-region.
- Gliomas expressed the SST2A mRNA splice variant.
- A 75-kDa SST2 protein was detected in glioma cell membranes, with weaker expression in normal astrocytes.
Conclusions:
- The somatostatin receptor SST2 is non-mutated in gliomas.
- SST2 in gliomas exhibits molecular properties similar to those in non-malignant cells.
- These findings support the investigation of SST2-targeted therapies for glioma treatment.