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Limited neuropeptide Y precursor processing in unfavourable metastatic neuroblastoma tumours

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 investig...

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Autores principales: Bjellerup, P, Theodorsson, E, Jörnvall, H, Kogner, P
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2000
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2363490/
https://www.ncbi.nlm.nih.gov/pubmed/10901366
http://dx.doi.org/10.1054/bjoc.2000.1234
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author Bjellerup, P
Theodorsson, E
Jörnvall, H
Kogner, P
author_facet Bjellerup, P
Theodorsson, E
Jörnvall, H
Kogner, P
author_sort Bjellerup, P
collection PubMed
description 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. © 2000 Cancer Research Campaign
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spelling pubmed-23634902009-09-10 Limited neuropeptide Y precursor processing in unfavourable metastatic neuroblastoma tumours Bjellerup, P Theodorsson, E Jörnvall, H Kogner, P Br J Cancer Regular Article 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. © 2000 Cancer Research Campaign Nature Publishing Group 2000-07 2000-06-15 /pmc/articles/PMC2363490/ /pubmed/10901366 http://dx.doi.org/10.1054/bjoc.2000.1234 Text en Copyright © 2000 Cancer Research Campaign https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Regular Article
Bjellerup, P
Theodorsson, E
Jörnvall, H
Kogner, P
Limited neuropeptide Y precursor processing in unfavourable metastatic neuroblastoma tumours
title Limited neuropeptide Y precursor processing in unfavourable metastatic neuroblastoma tumours
title_full Limited neuropeptide Y precursor processing in unfavourable metastatic neuroblastoma tumours
title_fullStr Limited neuropeptide Y precursor processing in unfavourable metastatic neuroblastoma tumours
title_full_unstemmed Limited neuropeptide Y precursor processing in unfavourable metastatic neuroblastoma tumours
title_short Limited neuropeptide Y precursor processing in unfavourable metastatic neuroblastoma tumours
title_sort limited neuropeptide y precursor processing in unfavourable metastatic neuroblastoma tumours
topic Regular Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2363490/
https://www.ncbi.nlm.nih.gov/pubmed/10901366
http://dx.doi.org/10.1054/bjoc.2000.1234
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