MiR- 16Regulates Crosstalk in NF-κB Inflammatory Signaling between Myeloma Cells and Bone Marrow Macrophages

Introduction:Multiple myeloma plasma cells (MM-PCs) home to and dynamically interact with the bone marrow (BM) microenvironment (BM-ME). Of the different factors secreted by the BM-ME, NF-κB-induced cytokines including IL-6 play a central role in MM-PC survival and resistance to treatments. Previously published data have shown that in the BM of MM patients the presence of CD163+ tumor associated macrophages (TAM) correlates with IL-6 production. The canonical NF-κB pathway is induced by most physiological stimuli to produce low levels of inflammatory cytokines, through the activation of the IκB kinase complex (IKKβ, IKKα, and IKKγ). This pathway seems constitutively activated in TAM, where instead the activation of the non-canonical pathway seems to play a critical role in the anti-cancer phenotype of BM macrophages (BM-Mϕ).