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

Liesbeth Bieghs, Malene Brohus, Ida B Kristensen, Niels Abildgaard, Martin Bøgsted, Hans E Johnsen, Cheryl A Conover, Elke De Bruyne, Karin Vanderkerken, Michael T Overgaard, Mette Nyegaard

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

234 Downloads (Pure)

Abstract

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.

OriginalsprogEngelsk
Artikelnummere0154256
TidsskriftPLOS ONE
Vol/bind11
Udgave nummer4
Antal sider10
ISSN1932-6203
DOI
StatusUdgivet - 2016

Fingeraftryk

Dyk ned i forskningsemnerne om 'Abnormal IGF-Binding Protein Profile in the Bone Marrow of Multiple Myeloma Patients'. Sammen danner de et unikt fingeraftryk.

Citationsformater