Somatostatin inhibits the production of vascular endothelial growth factorin human glioma cells

In various cell types, the neuro- and endocrine peptide somatostatin induce s inhibitory and anti-secretory effects. Since somatostatin receptors, espe cially of the subtype sst2A, are constantly over-expressed in gliomas, we i nvestigated the influence of somatostatin and the receptor subtype-selectiv e peptide/non-peptide agonists octreotide and L-054,522 on the secretion of the most important angiogenesis factor produced by gliomas, vascular endot helial growth factor (VEGF). Cultivated cells from solid human gliomas of d ifferent stages and glioma cell lines secreted variable amounts of VEGF, wh ich could be lowered to 25% to 80% by co-incubation with somatostatin or ss t2-selective agonists (octreotide and L-054,522). These effects were dose-d ependent at nanomolar concentrations, Stimulation with different growth fac tors (ECF, bFGF) or hypoxia considerably increased VEGF production over bas al levels. Growth factor-induced VEGF synthesis could be suppressed to < 50 % by co-incubation with somatostatin or an sst2-selective agonist; this was less pronounced in hypoxia-induced VEGF synthesis. The effects were detect ed at the protein and mRNA levels. These experiments indicate a potent anti -secretory action of somatostatin or sst2 agonists on human glioma cells th at may be useful for inhibiting angiogenesis in these tumors. (C) 2001 Wile y-Liss, Inc.