Development of immunotherapy against the bone destructive tumor

多发性骨髓瘤（MM）会对骨骼造成毁灭性的破坏。我们最近报道了单核细胞中TNFα转换酶（TACE）的表达会破坏其表面M-CSF受体（M-CSFR），从而严重破坏破骨细胞的形成（Blood, 2009）。由于TACE活性被TIMP3抑制，我们探索了骨髓间充质干细胞来源的TIMP3在MM单核细胞分化为DC或OC中的作用。本研究阐明了MM骨髓微环境中过量产生的TIMP3恢复单核细胞表面M-CSFR，促进其下游信号传导，从而导致MM广泛的骨破坏和DC分化受损。因此TIMP3可能成为MM骨病治疗的新靶点。

Multiple myeloma (MM) generates devastating bone destruction. We recently reported that TNFα converting enzyme (TACE) expression in monocytes cleaved their surface M-CSF receptor (M-CSFR), which drastically disrupts osteoclastogenesis（Blood, 2009）. Because TACE activity is inhibited by TIMP3, we explored the role of BMSC-derived TIMP3 in monocytic differentiation into DC or OC in MM. This study clarified that TIMP3 over-produced in MM bone marrow microenvironment restores surface M-CSFR on monocytes to facilitate their downstream signaling, which causes extensive bone destruction and impaired DC differentiation in MM. TIMP3 may therefore become a novel target in the treatment of MM bone disease.