R. Mentlein et al., Somatostatin inhibits the production of vascular endothelial growth factorin human glioma cells, INT J CANC, 92(4), 2001, pp. 545-550
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.