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

Katrin Brandt, Jing Wang, Kerstin Lundell, Marie Stahlberg, Henrik von Horn, Ewa Ehrenborg, Kerstin Hall, Hans Jornvall, Moira Lewitt

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Abstract

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 13 kDa but an apparent mass of 21 kDa on SDS-PAGE. A C-terminal fragment (IGFBP-1(131-234)) produced in vitro migrated at 11.4 kDa, close to its predicted size. However a C-terminal fragment of cleaved IGFBP-1 (IGFBP-1(142-234)) migrated at 14 kDa 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. (C) 2009 Elsevier Ltd. All rights reserved.
Original languageEnglish
Pages (from-to)507-512
JournalGrowth Hormone & IGF Research
Volume19
Issue number6
DOIs
Publication statusPublished - Dec 2009

Keywords

  • Insulin-like growth factor
  • IGF-binding protein-1
  • Azurocidin/heparin binding protein/CAP37
  • IGFBP protease
  • Multiple myeloma

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