Somatostatin receptors in gliomas

Gliomas differ from non-malignant glial cells in the overexpression or muta tions of genes involved in cell cycle or growth regulation. One example is the overexpression of the somatostatin receptor subtype 2 (sst2), especiall y 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 inte rnalised upon agonist stimulation. Immunoelectronmicroscopic studies show t hat the activated sst2 is internalised via caveolin-positive endosomal vesi cles and later accumulates in murtivesicular bodies and lysosomal compartme nts. The activated sst2 is found to be co-localised with the inhibitory G-p rotein Gi alpha at the plasma membrane and in early endosomal vesicles. Mul tiple signal transduction pathways are induced. Stimulation of sst2 lowers cAMP levels elicited by forskolin and activates the protein tyrosine phosph atase SHP-2. In contrast to other sst2-expressing cells a long term antipro lferative effect of somatostatin or sst2-selective agonists are not detecte d in cultivated glioma cells. However, continuous stimulation of sst2 decre ases the expression of genes promoting tumour survival. (C) 2000 Elsevier S cience Ltd. Published by Editions scientifiques et medicares Elsevier SAS.