Wnts induce migration and invasion of rnyeloma plasma cells
Wnts induce migration and invasion of rnyeloma plasma cells
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DOI：
10.1182/blood-2005-01-0049
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发表时间：
2005-09-01
期刊：
影响因子：
20.3
通讯作者：
Rudikoff, S
中科院分区：
文献类型：
--
作者：
Qiang, YW;Walsh, K;Rudikoff, S
多发性骨髓瘤是一种无法治愈的淋巴癌，其特征是骨髓腔中肿瘤性浆细胞的积累。关于调节骨髓瘤细胞在骨髓内运动和转移到继发部位的机制知之甚少。在此，我们鉴定了 wingless/int (Wnt) 家族的多个成员作为骨髓瘤细胞迁移/侵袭的启动子。 Wnt 介导的迁移与 Wnt/RhoA 途径相关，并且不需要通过 β-连环蛋白进行信号传导。诱导迁移需要激活 RhoA 和蛋白激酶 C (PKC) 家族成员，包括 PKC α、PKC β 和 PKC mu。活化的 RhoA 和 PKC α、PKC β 和 PKC mu 似乎在与细胞膜相关的大分子信号复合物中组装。这些结果表明骨髓瘤浆细胞的 Wnt 反应性可能是疾病进展的重要因素。
Multiple myeloma is an incurable form of lymphoid cancer characterized by accumulation of neoplastic plasma cells in the bone marrow cavity. Little is known about the mechanisms regulating myeloma cell movement within the bone marrow and metastasis to secondary sites. Herein, we identify multiple members of the wingless/ int (Wnt) family as promoters of myeloma cell migration/invasion. Wnt-mediated migration was associated with the Wnt/ RhoA pathway and did not necessitate signaling through beta-catenin. Activation of both RhoA and members of the protein kinase C (PKC) family, including PKC alpha, PKC beta, and PKC mu, were required for induction of migration. Activated RhoA and PKC alpha, PKC beta, and PKC mu appear to assemble in macromolecular signaling complexes that are associated with the cell membrane. These results suggest that Wnt responsiveness of myeloma plasma cells may be a significant factor in disease progression.