The effect of marrow stromal cells on TRAF6 expression levels in myeloma cells

Tumor necrosis factor receptor-associated factor 6 (TRAF6) is an important E3 ubiquitin ligase, which is key to immunity. TRAF6 has been implicated in the invasive growth and metastasis of various types of cancer, including squamous cell carcinoma, gastric cancer, myelodysplastic syndromes and acute myeloid leukemia. In the present study, associations between multiple myeloma (MM) and TRAF6, its downstream component nuclear factor-κB (NF-κB) and bone marrow stromal cells (MSC) were investigated. The TRAF6 protein expression levels of 18 patients were positively correlated with the protein levels of β-2 microglobulin (r2=0.3472; P=0.01) and negatively correlated with albumin protein levels (r2=0.5494; P=0.0004). In vitro expression of the TRAF6 protein, phosphorylated transcription factor p65 and phosphorylated p100 in myeloma cell lines was induced by MSCs from patients with MM. In addition, the in vitro expression of TRAF6 was associated with an enhanced proliferation rate of myeloma cells, which was blocked by silencing TRAF6 using small interfering RNA. Due to the association between the TRAF6-NF-κB signaling pathway in myeloma cells and MSCs, this signaling pathway may be a useful prognostic and therapeutic target in myeloma.