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Abnormal IGF-Binding Protein Profile in the Bone Marrow of Multiple Myeloma Patients

Insulin-like growth factor (IGF) signalling plays a key role in homing, progression, and treatment resistance in multiple myeloma (MM). In the extracellular environment, the majority of IGF molecules are bound to one of six IGF-binding proteins (IGFBP1-6), leaving a minor fraction of total IGF free...

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Autores principales: Bieghs, Liesbeth, Brohus, Malene, Kristensen, Ida B., Abildgaard, Niels, Bøgsted, Martin, Johnsen, Hans E., Conover, Cheryl A., De Bruyne, Elke, Vanderkerken, Karin, Overgaard, Michael T., Nyegaard, Mette
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4844248/
https://www.ncbi.nlm.nih.gov/pubmed/27111220
http://dx.doi.org/10.1371/journal.pone.0154256
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author Bieghs, Liesbeth
Brohus, Malene
Kristensen, Ida B.
Abildgaard, Niels
Bøgsted, Martin
Johnsen, Hans E.
Conover, Cheryl A.
De Bruyne, Elke
Vanderkerken, Karin
Overgaard, Michael T.
Nyegaard, Mette
author_facet Bieghs, Liesbeth
Brohus, Malene
Kristensen, Ida B.
Abildgaard, Niels
Bøgsted, Martin
Johnsen, Hans E.
Conover, Cheryl A.
De Bruyne, Elke
Vanderkerken, Karin
Overgaard, Michael T.
Nyegaard, Mette
author_sort Bieghs, Liesbeth
collection PubMed
description Insulin-like growth factor (IGF) signalling plays a key role in homing, progression, and treatment resistance in multiple myeloma (MM). In the extracellular environment, the majority of IGF molecules are bound to one of six IGF-binding proteins (IGFBP1-6), leaving a minor fraction of total IGF free and accessible for receptor activation. In MM, high IGF-receptor type 1 expression levels correlate with a poor prognosis, but the status and role of IGF and IGFBPs in the pathobiology of MM is unknown. Here we measured total IGF1, IGF2, and intact IGFBP levels in blood and bone marrow samples from MM (n = 17), monoclonal gammopathy of undetermined significance (MGUS) (n = 37), and control individuals (n = 15), using ELISA (IGFs) and (125)I-IGF1 Western Ligand Blotting (IGFBPs). MGUS and MM patients displayed a significant increase in intact IGFBP-2 (2.5–3.8 fold) and decrease in intact IGFBP-3 (0.6–0.5 fold) in the circulation compared to control individuals. Further, IGFBP-2 as well as total IGFBP levels were significantly lower in bone marrow compared to circulation in MM and MGUS only, whereas IGF1, IGF2, and IGFBP-3 were equally distributed between the two compartments. In conclusion, the profound change in IGFBP profile strongly suggests an increased IGF bioavailability in the bone marrow microenvironment in MGUS and MM, despite no change in growth factor concentration.
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spelling pubmed-48442482016-05-05 Abnormal IGF-Binding Protein Profile in the Bone Marrow of Multiple Myeloma Patients Bieghs, Liesbeth Brohus, Malene Kristensen, Ida B. Abildgaard, Niels Bøgsted, Martin Johnsen, Hans E. Conover, Cheryl A. De Bruyne, Elke Vanderkerken, Karin Overgaard, Michael T. Nyegaard, Mette PLoS One Research Article Insulin-like growth factor (IGF) signalling plays a key role in homing, progression, and treatment resistance in multiple myeloma (MM). In the extracellular environment, the majority of IGF molecules are bound to one of six IGF-binding proteins (IGFBP1-6), leaving a minor fraction of total IGF free and accessible for receptor activation. In MM, high IGF-receptor type 1 expression levels correlate with a poor prognosis, but the status and role of IGF and IGFBPs in the pathobiology of MM is unknown. Here we measured total IGF1, IGF2, and intact IGFBP levels in blood and bone marrow samples from MM (n = 17), monoclonal gammopathy of undetermined significance (MGUS) (n = 37), and control individuals (n = 15), using ELISA (IGFs) and (125)I-IGF1 Western Ligand Blotting (IGFBPs). MGUS and MM patients displayed a significant increase in intact IGFBP-2 (2.5–3.8 fold) and decrease in intact IGFBP-3 (0.6–0.5 fold) in the circulation compared to control individuals. Further, IGFBP-2 as well as total IGFBP levels were significantly lower in bone marrow compared to circulation in MM and MGUS only, whereas IGF1, IGF2, and IGFBP-3 were equally distributed between the two compartments. In conclusion, the profound change in IGFBP profile strongly suggests an increased IGF bioavailability in the bone marrow microenvironment in MGUS and MM, despite no change in growth factor concentration. Public Library of Science 2016-04-25 /pmc/articles/PMC4844248/ /pubmed/27111220 http://dx.doi.org/10.1371/journal.pone.0154256 Text en © 2016 Bieghs et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Bieghs, Liesbeth
Brohus, Malene
Kristensen, Ida B.
Abildgaard, Niels
Bøgsted, Martin
Johnsen, Hans E.
Conover, Cheryl A.
De Bruyne, Elke
Vanderkerken, Karin
Overgaard, Michael T.
Nyegaard, Mette
Abnormal IGF-Binding Protein Profile in the Bone Marrow of Multiple Myeloma Patients
title Abnormal IGF-Binding Protein Profile in the Bone Marrow of Multiple Myeloma Patients
title_full Abnormal IGF-Binding Protein Profile in the Bone Marrow of Multiple Myeloma Patients
title_fullStr Abnormal IGF-Binding Protein Profile in the Bone Marrow of Multiple Myeloma Patients
title_full_unstemmed Abnormal IGF-Binding Protein Profile in the Bone Marrow of Multiple Myeloma Patients
title_short Abnormal IGF-Binding Protein Profile in the Bone Marrow of Multiple Myeloma Patients
title_sort abnormal igf-binding protein profile in the bone marrow of multiple myeloma patients
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4844248/
https://www.ncbi.nlm.nih.gov/pubmed/27111220
http://dx.doi.org/10.1371/journal.pone.0154256
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