Osteoclasts enhance myeloma cell growth and survival via cell-cell contact: a vicious cycle between bone destruction and myeloma expansion
Osteoclasts enhance myeloma cell growth and survival via cell-cell contact: a vicious cycle between bone destruction and myeloma expansion
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DOI：
10.1182/blood-2003-11-3839
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发表时间：
2004-10-15
期刊：
影响因子：
20.3
通讯作者：
Matsumoto, T
中科院分区：
文献类型：
--
作者：
Abe, M;Hiura, K;Matsumoto, T
多发性骨髓瘤（MM）在骨髓中扩张，并通过增强其附近的骨细胞骨吸收引起破坏性骨破坏，这表明MM细胞和破骨细胞（OC）之间存在密切的相互作用。在这里，我们表明，外周血单核细胞衍生的OC增强的生长和生存的原代MM细胞以及MM细胞系更有力地比基质细胞，和OC保护MM细胞的凋亡诱导的血清耗竭或阿霉素。OC产生骨桥蛋白（OPN）和白细胞介素6（IL-6），MM细胞与OC的粘附增加了OC产生的IL-6。此外，IL-6和OPN组合增强MM细胞生长和存活。然而，OC对MM细胞生长和存活的影响仅通过同时添加抗IL-6和抗OPN抗体而部分抑制，并且通过抑制MM细胞与OC之间的细胞接触而完全消除。这些结果表明，OC通过部分依赖于IL-6和OPN的细胞-细胞接触介导的机制增强MM细胞的生长和存活。这表明MM细胞与OC的相互作用增加MM生长和存活，从而形成恶性循环，导致广泛的骨破坏和MM细胞扩增。(C)2004年，美国血液学会。
Multiple myeloma (MM) expands in the bone marrow and causes devastating bone destruction by enhancing osteoclastic bone resorption in its vicinity, suggesting a close interaction between MM cells and osteoclasts (OCs). Here, we show that peripheral blood mononuclear cell-derived OCs enhanced growth and survival of primary MM cells as well as MM cell lines more potently than stromal cells, and that OCs protected MM cells from apoptosis induced by serum depletion or doxorubicin. OCs produced osteopontin (OPN) and interleukin 6 (IL-6), and adhesion of MM cells to OCs increased IL-6 production from OCs. In addition, IL-6 and OPN in combination enhanced MM cell growth and survival. However, the effects of OCs on MM cell growth and survival were only partially suppressed by a simultaneous addition of anti-IL-6 and anti-OPN antibodies and were completely abrogated by inhibition of cellular contact between MM cells and OCs. These results demonstrate that OCs enhance MM cell growth and survival through a cell-cell contact-mediated mechanism that is partially dependent on IL-6 and OPN. It is suggested that interactions of MM cells with OCs augment MM growth and survival and, thereby, form a vicious cycle, leading to extensive bone destruction and MM cell expansion. (C) 2004 by The American Society of Hematology.