Somatostatin inhibits the production of vascular endothelial growth factor in human glioma cells.

Abstract

In various cell types, the neuro- and endocrine peptide somatostatin induces inhibitory and anti-secretory effects. Since somatostatin receptors, especially of the subtype sst2A, are constantly over-expressed in gliomas, we investigated the influence of somatostatin and the receptor subtype-selective peptide/non-peptide agonists octreotide and L-054,522 on the secretion of the most important angiogenesis factor produced by gliomas, vascular endothelial growth factor (VEGF). Cultivated cells from solid human gliomas of different stages and glioma cell lines secreted variable amounts of VEGF, which could be lowered to 25% to 80% by co-incubation with somatostatin or sst2-selective agonists (octreotide and L-054,522). These effects were dose-dependent at nanomolar concentrations. Stimulation with different growth factors (EGF, bFGF) or hypoxia considerably increased VEGF production over basal 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 detected at the protein and mRNA levels. These experiments indicate a potent anti-secretory action of somatostatin or sst2 agonists on human glioma cells that may be useful for inhibiting angiogenesis in these tumors.

• Authors: R Mentlein, O Eichler, F Forstreuter, J Held-Feindt
• Journal: International journal of cancer (Int J Cancer) Vol. 92 Issue 4 Pg. 545-50 (May 15 2001) ISSN: 0020-7136 [Print] United States
• PMID: 11304689 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Hormonal
• Benzimidazoles
• Endothelial Growth Factors
• Hormones
• Indoles
• L 054522
• Lymphokines
• Peptides
• RNA, Messenger
• Vascular Endothelial Growth Factor A
• Vascular Endothelial Growth Factors
• Fibroblast Growth Factor 2
• Somatostatin
• Epidermal Growth Factor
• DNA
• Octreotide

Topics

• Antineoplastic Agents, Hormonal (pharmacology)
• Benzimidazoles (pharmacology)
• Blotting, Northern
• Brain Neoplasms (metabolism)
• Cells, Cultured
• DNA (metabolism)
• Dose-Response Relationship, Drug
• Endothelial Growth Factors (biosynthesis, metabolism)
• Epidermal Growth Factor (pharmacology)
• Fibroblast Growth Factor 2 (pharmacology)
• Glioma (metabolism)
• Hormones (pharmacology)
• Humans
• Hypoxia
• Indoles (pharmacology)
• Lymphokines (biosynthesis, metabolism)
• Octreotide (pharmacology)
• Peptides (chemistry)
• RNA, Messenger (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Somatostatin (agonists, pharmacology)
• Tumor Cells, Cultured
• Vascular Endothelial Growth Factor A
• Vascular Endothelial Growth Factors