IGFBP-1 protease activity and IGFBP-1 fragments in a patient with multiple myeloma.


OBJECTIVE Cleavage of IGFBPs by proteases results in IGFBP fragments that have altered IGF-binding affinity, and IGF-independent roles. We have previously purified a specific IGFBP-1 protease activity from the urine of an individual with multiple myeloma and dermatitis. The aim of this study was to determine whether IGFBP-1 protease activity and/or IGFBP-1 fragments were present in the circulation of this patient. METHODS The size of immunoreactive IGFBP-1 in serum samples was determined after Superose 12 chromatography. Intact IGFBP-1 and IGFBP-1 fragments were characterized in four RIAs and after SDS-PAGE. RESULTS Specific proteolysis of IGFBP-1 generated an N-terminal fragment (IGFBP-1(1-130)) with a predicted molecular mass of 13kDa but an apparent mass of 21kDa on SDS-PAGE. A C-terminal fragment (IGFBP-1(131-234)) produced in vitro migrated at 11.4kDa, close to its predicted size. However a C-terminal fragment of cleaved IGFBP-1 (IGFBP-1(142-234)) migrated at 14kDa on SDS-PAGE. Serum from the patient inhibited IGFBP-1 protease activity. Immunoreactive IGFBP-1 in patient serum was present at molecular masses consistent with IGFBP-1 fragments, in addition to intact IGFBP-1. CONCLUSIONS Specific cleavage of IGFBP-1 occurs at the tissue level and not in the circulation in a patient with multiple myeloma and dermatitis. The fragments that are generated may have endocrine roles.

DOI: 10.1016/j.ghir.2009.05.002

Cite this paper

@article{Brandt2009IGFBP1PA, title={IGFBP-1 protease activity and IGFBP-1 fragments in a patient with multiple myeloma.}, author={Katrin Brandt and Jing Wang and Kerstin Lundell and Marie St{\aa}hlberg and Henrik von Horn and Ewa E Ehrenborg and Kerstin E Hall and Hans J{\"{o}rnvall and Moira S. Lewitt}, journal={Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society}, year={2009}, volume={19 6}, pages={507-12} }