Figure 9
A model for the role of TNFα in pathophysiology of MM. TNFα secreted from MM cells induces modest proliferation, as well as MEK/MAPK and NF-κB activation, in MM cells. It also augments IL-6 secretion, as well as activates MEK/MAPK and NF-κB, in BMSCs. Importantly, TNFα upregulates expression of CD49d (VLA-4), CD11a (LFA-1), and Muc-1 on MM.1S cells; as well as CD54 (ICAM-1) and CD106 (VCAM-1) on BMSCs, which is mediated via NF-κB activation. Upregulation of these adhesion molecules on MM cells and BMSCs by TNFα results in increased MM cell binding to BMSCs, with an associated induction of the MM cell growth and survival factor IL-6. The proteasome inhibitor PS-341 abrogates this response
