title: Decorin is down-regulated in multiple myeloma and MGUS bone marrow plasma and inhibits HGF-induced myeloma plasma cell viability and migration.
abstract: OBJECTIVE
  Decorin is a stromal-produced small leucine-rich proteoglycan known to attenuate tumour pro-survival, migration, proliferation and angiogenic signalling pathways. Recent studies have shown that decorin interacts with the hepatocyte growth factor (HGF) receptor c-Met, a potential key pathway in multiple myeloma (MM).
  
  
  METHODS
  Decorin levels in paired peripheral blood and bone marrow plasma samples from healthy volunteers (HV) (n = 23), and patients with monoclonal gammopathy of undetermined significance (MGUS) (n = 41) and MM (n = 19) were determined by ELISA. Further, the ability of decorin to inhibit HGF-induced effects on MM cell lines were analysed in vitro using cell viability and Transwell migration assays.
  
  
  RESULTS
  We found that decorin concentrations were significantly higher (P < 0.05) in bone marrow (BM) plasma from HVs (median 35.2 ng/mL; range, 15.3-99.1) compared with MGUS (median 22.5 ng/mL; range, 11.1-59.5) and patients with MM (median 21.5 ng/mL; range, 10.6-35.9). Decorin levels were higher in BM plasma than in peripheral blood in all groups, with a BM/PB ratio of 3.9, 3.4 and 2.5 for HV, MGUS and MM, respectively. A positive correlation (Spearman's ρ = 0.51, P < 0.05) was found between simultaneously measured levels of HGF and decorin in BM plasma in HVs, but not in MGUS or MM samples. Functionally, decorin inhibited HGF-induced migration and viability of INA-6 and ANBL-6 MM cell lines, independent of c-Met down-regulation.
  
  
  CONCLUSIONS
  Our results show that decorin is down-regulated in MGUS and MM bone marrow plasma and that it inhibits HGF-induced viability and migration of myeloma cell lines in vitro.
authors.affiliation: Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.|Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.|Department of Haematology, Odense University Hospital, Odense, Denmark.
authors.forename: Ida B
authors.initials: IB
authors.lastname: Kristensen
authors.affiliation: Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark.
authors.forename: Lise
authors.initials: L
authors.lastname: Pedersen
authors.affiliation: Department of Cancer Research and Molecular Medicine, K.G. Jebsen Centre of Myeloma Research, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Torstein B
authors.initials: TB
authors.lastname: Rø
authors.affiliation: Department of Haematology, Odense University Hospital, Odense, Denmark.
authors.forename: Jacob H
authors.initials: JH
authors.lastname: Christensen
authors.affiliation: Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
authors.forename: Maria B
authors.initials: MB
authors.lastname: Lyng
authors.affiliation: Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.|Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark.
authors.forename: Lars M
authors.initials: LM
authors.lastname: Rasmussen
authors.affiliation: Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.|Department of Oncology, Odense University Hospital, Odense, Denmark.
authors.forename: Henrik J
authors.initials: HJ
authors.lastname: Ditzel
authors.affiliation: Department of Cancer Research and Molecular Medicine, K.G. Jebsen Centre of Myeloma Research, Norwegian University of Science and Technology, Trondheim, Norway.|Department of Immunology and Transfusion Medicine, St. Olavs University Hospital, Trondheim, Norway.
authors.forename: Magne
authors.initials: M
authors.lastname: Børset
authors.affiliation: Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.|Department of Haematology, Odense University Hospital, Odense, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Abildgaard
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D058575:Decorin / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008998:Monoclonal Gammopathy of Undetermined Significance / Q000378:metabolism*; D009101:Multiple Myeloma / Q000378:metabolism*; D010950:Plasma Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism
chemical_list: D058575:Decorin; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met
keywords: MGUS; bone marrow; decorin; hepatocyte growth factor; multiple myeloma