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Letters to the Editor
TGF-β is released from the bone matrices through enhanced bone resorption, and activated by an acid and matrix metalloproteinases secreted from OC. Consistently, the phosphorylation of Smad2 was increased in MM tumor lesions in immobilized hind legs by sciatic denervation (Figure 3B), which may in part contribute to the further activation of TAK1 in MM lesions under mechanical unloading with enhanced osteoclastogenesis. Importantly, treatment with the
TAK1 inhibitor LL-Z1640-2 as well as the PIM inhibitor SMI16a was able to efficaciously reduce MM growth enhancement in the immobilized hind legs (Figure 3A), suggesting the therapeutic efficacy of these inhibitors under mechanical unloading. We are currently studying the therapeutic efficacy of LL-Z1640-2 and SMI16a in combination with proteasome inhibitors to maximize their anabolic as well as antitumor effects against MM.
In addition, we noticed that multiple palpable solid
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Figure 3. Legend on following page.
haematologica | 2022; 107(3)
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