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Updated: Oct 10, 2026
Evaluation of Biomarkers in Glioma by Immunohistochemistry on Paraffin-Embedded 3D Glioma Neurosphere Cultures
Published on: January 9, 2019
Somatostatin receptors in gliomas
J Held-Feindt1, B Krisch, F Forstreuter
1Department of Anatomy, University of Kiel, Germany. held-feindt@anat.uni-kiel.de
Abstract:
Gliomas differ from non-malignant glial cells in the overexpression or mutations of genes involved in cell cycle or growth regulation. One example is the overexpression of the somatostatin receptor subtype 2 (sst2), especially of the splice variant sst2A. The reasons for this overexpression are not known. However, the coding sequence and part of the promoter region is not mutated. In accordance to this, the sst2 is functionally active and is internalised upon agonist stimulation. Immunoelectronmicroscopic studies show that the activated sst2 is internalised via caveolin-positive endosomal vesicles and later accumulates in multivesicular bodies and lysosomal compartments. The activated sst2 is found to be co-localised with the inhibitory G-protein Gialpha at the plasma membrane and in early endosomal vesicles. Multiple signal transduction pathways are induced. Stimulation of sst2 lowers cAMP levels elicited by forskolin and activates the protein tyrosine phosphatase SHP-2. In contrast to other sst2-expressing cells a long term antiproliferative effect of somatostatin or sst2-selective agonists are not detected in cultivated glioma cells. However, continuous stimulation of sst2 decreases the expression of genes promoting tumour survival.
Insights
Glioma cells overexpress somatostatin receptor subtype 2 (sst2), which is functionally active. Continuous sst2 stimulation decreases genes promoting tumor survival, despite lacking antiproliferative effects.
Area of Science:
- Neuro-oncology
- Molecular biology
- Cell signaling
Background:
- Gliomas exhibit altered gene expression in cell cycle and growth regulation compared to normal glial cells.
- Somatostatin receptor subtype 2 (sst2), particularly the sst2A splice variant, is overexpressed in gliomas.
- The underlying reasons for sst2 overexpression in gliomas remain unclear, though the gene sequence is not mutated.
Purpose of the Study:
- To investigate the functional activity and signaling pathways of somatostatin receptor subtype 2 (sst2) in glioma cells.
- To understand the cellular trafficking and downstream effects of activated sst2 in the context of glioma.
Main Methods:
- Immunoelectron microscopy to visualize sst2 localization and trafficking.
- Agonist stimulation to activate sst2 and assess downstream signaling.
- Analysis of co-localization with specific proteins like Gialpha and SHP-2.
- Measurement of cAMP levels and gene expression changes.
Main Results:
- Activated sst2 is internalized via caveolin-positive vesicles and accumulates in endosomal and lysosomal compartments.
- Co-localization of activated sst2 with Gialpha at the plasma membrane and early endosomes.
- Stimulation of sst2 leads to decreased cAMP levels and activation of SHP-2.
- Continuous sst2 stimulation reduces the expression of genes that promote tumor survival, though direct antiproliferative effects are not observed.
Conclusions:
- Overexpressed sst2 in gliomas is functionally active and undergoes specific internalization and trafficking pathways.
- Sst2 activation induces distinct signaling cascades, including modulation of cAMP and SHP-2.
- While not directly antiproliferative, sst2 signaling in gliomas can impact tumor survival pathways.
