Development of immunotherapy against the bone destructive tumor

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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.