Upregulation of Syndecan-1 in the bone marrow microenvironment in multiple myeloma is associated with angiogenesis.

Abstract

Syndecan-1 (SDC1), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF) and interleukin-6 (IL6) are expressed by malignant plasma cells and cells in the bone marrow microenvironment and may be involved in the angiogenic process in multiple myeloma (MM). In this study, we examined the association between bone marrow angiogenesis estimated as micro-vessel density (MVD) and gene expression of SDC1, HGF, VEGF and IL6 in whole bone marrow biopsies from healthy volunteers (n = 10), patients with monoclonal gammopathy of undetermined significance (MGUS) (n = 35) and MM (n = 65). MVD was significantly higher in patients with MM than MGUS (P = 0.03) and was positively correlated with plasma cell percentage (P = 0.002). SDC1 gene expression increased with increasing MVD in patients with MGUS and MM (P < 0.001). A positive correlation between bone marrow plasma cell percentage and SDC1 gene expression was detected in patients with MM (P < 0.001). Importantly, after adjustment for plasma cell percentage, the association between MVD and SDC1 gene expression remained significant (P = 0.026). No association between bone marrow angiogenesis and gene expression of HGF, VEGF and IL6 was seen. Our study indicates that SDC1 expressed by the bone marrow microenvironment is involved in angiogenesis in MM.