Expression and precursor processing of neuropeptide Y in human pheochromocytoma and neuroblastoma tumors.
The expression of the potent vasoactive peptide neuropeptide Y (NPY) was studied in 16 clinically and/or histologically diagnosed human pheochromocytomas and 3 human neuroblastoma tumors. All tumors contained NPY in concentrations ranging from 21 pmol/g of tissue, similar to that found in normal adrenal tissue, to 91,000 pmol/g (median, 1,700 pmol/g). Three control tumors of Cushing's type did not contain NPY. An almost total proteolytic processing of pro-NPY to normal NPY was observed in the tumors (median, 93%; range, 72-100%). A positive correlation between the processing efficiency and the NPY content was also observed. The small amount of pro-NPY found in the tumors was characterized by "in vitro conversion" with endoproteinase Lys-C. In the tumor extracts, the majority of the NPY immunoreactivity, corresponding in size to the NPY standard, also behaved like synthetic NPY by high performance liquid chromatography and isoelectric focusing. As assessed by both its elution position in isoelectric focusing and its reaction with an antiserum specific for the COOH-terminal amidated sequence, the peptide produced by the tumors was found to be efficiently amidated, a modification which is essential for the biological activity of NPY. It is concluded that although only a subset of chromaffin cells express NPY, a very high number of pheochromocytomas and neuroblastomas produce correctly amidated and thus biologically active NPY in large amounts, and that this is of potential importance for tumor-related cardiovascular symptoms and for autocrine stimulation of tumor cells.
O'Hare
M M
MM
University Department of Clinical Chemistry, Rigshospitalet, Copenhagen, Denmark.
Schwartz
T W
TW
D000293:Adolescent; D000302:Adrenal Cortex / Q000378:metabolism; D000310:Adrenal Gland Neoplasms / Q000378:metabolism*; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007525:Isoelectric Focusing; D008297:Male; D008875:Middle Aged; D009447:Neuroblastoma / Q000378:metabolism*; D009478:Neuropeptide Y / Q000378:metabolism*; D010673:Pheochromocytoma / Q000378:metabolism*; D011498:Protein Precursors / Q000378:metabolism*; D011863:Radioimmunoassay
D009478:Neuropeptide Y; D011498:Protein Precursors