Production and secretion of neuropeptides by nervous system tumors

Information about the production of neuropeptides by intracranial tumors, such as gliomas and meningiomas, is limited. There is, however, accumulating evidence that indicates the production of some neuropeptides by these tumors. In this review article, we focus on three peptides: endothelin- 1, pituitary adenylate cyclase activating polypeptide and adrenomedullin. Endothelin-1 is a potent vasoconstrictor peptide originally discovered in aortic endothelial cells. Pituitary adenylate cyclase activating polypeptide is a neuropeptide isolated from ovine hypothalamus, as a result of its ability to stimulate adenylate cyclase activity in rat pituitary. Adrenomedullin is a potent vasodilator peptide isolated from human pheochromocytoma. Endothelin-1, pituitary adenylate cyclase activating polypeptide and adrenomedullin are present in the brain. In addition, it has been shown that all three peptides are produced by human gliomas and other brain tumors. Interestingly, gliomas express receptors for their respective peptides, which have biological actions on proliferation and/or differentiation of tumor cells. Thus, these three peptides seem to act as paracrine or autocrine growth regulators for tumors. These findings raise the possibility of new strategies for the treatment of nervous system tumors, such as the blockade of the peptide actions using specific peptide antagonists.