核心蛋白聚糖在多发性骨髓瘤和意义未明的单克隆丙种球蛋白血症骨髓血浆中表达下调，并抑制 HGF 诱导的骨髓瘤浆细胞活力和迁移。

Decorin is down-regulated in multiple myeloma and MGUS bone marrow plasma and inhibits HGF-induced myeloma plasma cell viability and migration.

机构信息

Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.

Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.

出版信息

Eur J Haematol. 2013 Sep;91(3):196-200. doi: 10.1111/ejh.12125. Epub 2013 Jul 7.

DOI:10.1111/ejh.12125

PMID:23607294

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.

摘要

目的

核心蛋白聚糖是一种基质产生的富含亮氨酸的小蛋白聚糖，已知可减弱肿瘤的生存、迁移、增殖和血管生成信号通路。最近的研究表明，核心蛋白聚糖与肝细胞生长因子（HGF）受体 c-Met 相互作用，c-Met 是多发性骨髓瘤（MM）中的一个潜在关键途径。

方法

通过 ELISA 测定来自健康志愿者（HV）（n=23）、单克隆丙种球蛋白病不确定意义（MGUS）（n=41）和 MM（n=19）的配对外周血和骨髓血浆样本中的核心蛋白聚糖水平。此外，还在体外使用细胞活力和 Transwell 迁移测定分析了核心蛋白聚糖抑制 HGF 诱导的 MM 细胞系的能力。

结果

我们发现 HV 的骨髓（BM）血浆中的核心蛋白聚糖浓度明显更高（P<0.05）（中位数 35.2ng/mL；范围 15.3-99.1），与 MGUS（中位数 22.5ng/mL；范围 11.1-59.5）和 MM 患者（中位数 21.5ng/mL；范围 10.6-35.9）相比。在所有组中，BM 血浆中的核心蛋白聚糖水平均高于外周血，HV、MGUS 和 MM 的 BM/PB 比值分别为 3.9、3.4 和 2.5。在 HV 的 BM 血浆中同时测量到 HGF 和核心蛋白聚糖水平之间存在正相关（Spearman's ρ=0.51，P<0.05），但在 MGUS 或 MM 样本中则没有。功能上，核心蛋白聚糖抑制 HGF 诱导的 INA-6 和 ANBL-6 MM 细胞系的迁移和活力，而与 c-Met 下调无关。