title: Limited neuropeptide Y precursor processing in unfavourable metastatic neuroblastoma tumours.
abstract: Neuropeptide Y (NPY) is found at high concentrations in neural crest-derived 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 investigated for different molecular forms of NPY and for significance of proNPY processing. Gel-permeation chromatography identified intact NPY (1-36) in all tumours, whereas proNPY (69 amino acids) was detected only in control adrenal tissue and malignant neuroblastomas. Purification of NPY-like immunoreactivity in tumour extracts and structural characterization revealed that both 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 neuroblastomas 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 tumours (n = 12), (93%; 69-100%), (P= 0.012). ProNPY processing of less than 50% was correlated with poor clinical outcome (P = 0.004). MYCN oncogene amplification 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 generated molecular forms of NPY with known differences in NPY-receptor selectivity, implicating a potential for in vivo modulation of NPY-like effects in tumour tissue.
authors.affiliation: Department of Clinical Chemistry, Karolinska Institutet and Karolinska Hospital, Stockholm, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Bjellerup
authors.forename: E
authors.initials: E
authors.lastname: Theodorsson
authors.forename: H
authors.initials: H
authors.lastname: Jörnvall
authors.forename: P
authors.initials: P
authors.lastname: Kogner
mesh_terms: D002648:Child; D002675:Child, Preschool; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D013058:Mass Spectrometry; D009447:Neuroblastoma / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D009478:Neuropeptide Y / Q000032:analysis / Q000378:metabolism*; D010446:Peptide Fragments / Q000032:analysis; D011498:Protein Precursors / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D017421:Sequence Analysis; D015996:Survival Rate
chemical_list: D009478:Neuropeptide Y; D010446:Peptide Fragments; D011498:Protein Precursors; C113547:neuropeptide Y (3-36)