Metabolic Activity of Neural Crest Tumours in Tissue Culture

Abstract

NUMEROUS reports have described the raised urinary excretion of metabolites of norepinephrine, and its precursors, by children with tumours of neural crest origin^1–7. It has also been observed that many of these patients show increased norepinephrine production but produce little or no physiological evidence of increased secretion of this potent catecholamine. Some possible explanations for this apparent paradox are as follows: (1) There might be an adaptation to increased blood-levels of norepinephrine. (2) The norepinephrine might be inactivated within the tumour before release into the blood. (3) A combination of the foregoing two mechanisms might be acting. (4) The rate of inactivation of norepinephrine in tissues other than the tumour (liver, kidney, etc.) might be increased. In a previous investigation, La Brosse and Karon have presented evidence that neural crest tumours contain catechol-O-methyltransferase (COMT) activity⁸. Since the 3-O-methylated product of norepinephrine has been shown by Evarts et al.⁹ to be physiologically inactive in comparison with norepinephrine, the finding that COMT activity existed within the tumour indicated that, at least in some cases, norepinephrine may be inactivated before being released into the blood.