Ida B Kristensen1,2,3, Lise Pedersen4, Torstein B Rø5, Jacob H Christensen3, Maria B Lyng2, Lars M Rasmussen1,4, Henrik J Ditzel2,6, Magne Børset5,7, Niels Abildgaard1,3. 1. Institute of Clinical Research, University of Southern Denmark, Odense, Denmark. 2. Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark. 3. Department of Haematology, Odense University Hospital, Odense, Denmark. 4. Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark. 5. Department of Cancer Research and Molecular Medicine, K.G. Jebsen Centre of Myeloma Research, Norwegian University of Science and Technology, Trondheim, Norway. 6. Department of Oncology, Odense University Hospital, Odense, Denmark. 7. Department of Immunology and Transfusion Medicine, St. Olavs University Hospital, Trondheim, Norway.
Abstract
OBJECTIVES: 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. CONCLUSION: 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.
OBJECTIVES: 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. CONCLUSION: 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: 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 Journal: PLoS One Date: 2016-04-25 Impact factor: 3.240