Limited neuropeptide Y precursor processing in unfavourable metastatic neuroblastoma tumours

Neuropeptide Y (NPY) is found at high concentrations in neural crest-derive d tumours and has been implicated as a regulatory peptide in tumour growth and differentiation. Neuroblastomas, ganglioneuromas and phaeochromocytomas with significant concentrations of NPY-like immunoreactivity were investig ated for different molecular forms of NPY and for significance of proNPY pr ocessing. Gel-permeation chromatography identified intact NPY (1-36) in all tumours, whereas proNPY (69 amino acids) was detected only in control adre nal tissue and malignant neuroblastomas. Purification of NPY-like immunorea ctivity in tumour extracts and structural characterization revealed that bo th NPY (1-36) and the truncated form NPY (3-36) was present. The degree of processing of proNPY to NPY in tumour tissue was lower in advanced neurobla stomas with regional or metastatic spread (stage 3 and 4) (n = 6), (41%, 12 -100%, median, range), compared to the less aggressive stage 1, 2 and 4S tu mours (n = 12), (93%; 69-100%), (P=0.012). ProNPY processing of less than 5 0% was correlated with poor clinical outcome (P=0.004). MYCN oncogene ampli fication was also correlated to a low degree of proNPY processing (P=0.025) . In summary, a low degree of proNPY processing was correlated to clinical advanced stage and poor outcome in neuroblastomas. ProNPY/NPY processing ge nerated molecular forms of NPY with known differences in NPY-receptor selec tivity, implicating a potential for in vivo modulation of NPY-like effects in tumour tissue. (C) 2000 Cancer Research Campaign.