Article open access publication

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

PLoS ONE, Public Library of Science (PLoS), ISSN 1932-6203

Volume 11, 4, 2016

DOI:10.1371/journal.pone.0154256, Dimensions: pub.1045926373, PMC: PMC4844248, PMID: 27111220,

Affiliations

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  1. (1) Aarhus University, grid.7048.b, AU
  2. (2) Department of Hematology, Aalborg Hospital, Aalborg University, Alborg, Denmark
  3. (3) Vrije Universiteit Brussel, grid.8767.e
  4. (4) Aalborg University, grid.5117.2, AAU
  5. (5) Odense University Hospital, grid.7143.1, Southern Denmark Region
  6. (6) Mayo Clinic, grid.66875.3a

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 125I-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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Times Cited: 5

Field Citation Ratio (FCR): 2.18

Relative Citation ratio (RCR): 0.34

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