IL-8 secreted in a macrophage migration-inhibitory factor- and CD74-dependent manner regulates B cell chronic lymphocytic leukemia survival
IL-8 secreted in a macrophage migration-inhibitory factor- and CD74-dependent manner regulates B cell chronic lymphocytic leukemia survival
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DOI：
10.1073/pnas.0701553104
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发表时间：
2007-08-14
影响因子：
11.1
通讯作者：
Shachar, Idit
中科院分区：
文献类型：
--
作者：
Binsky, Inbal;Haran, Michal;Shachar, Idit
慢性淋巴细胞白血病（CLL）是一种小成熟淋巴细胞的恶性疾病。以往的研究表明，与正常B细胞相比，CLL B淋巴细胞表达相对较多的CD74 mRNA。在本研究中，我们分析了CD74在B-CLL细胞中调控的分子机制。本研究的结果表明，细胞表面CD74的激活，在疾病早期通过其天然配体巨噬细胞迁移抑制因子（MIF）高水平表达，启动了促进肿瘤进展的信号级联反应。该途径诱导NF-kappa B活化，导致IL-8分泌，进而促进细胞存活。抑制这一途径导致细胞存活率降低。这些发现可以形成独特的治疗策略的基础，旨在阻断cd74诱导的，IL-8依赖的生存途径。
Chronic lymphocytic leukemia (CLL) is a malignant disease of small mature lymphocytes. Previous studies have shown that CLL B lymphocytes express relatively large amounts of CD74 mRNA relative to normal B cells. In the present study, we analyzed the molecular mechanism regulated by CD74 in B-CLL cells. The results presented here show that activation of cell-surface CD74, expressed at high levels from an early stage of the disease by its natural ligand, macrophage migration-inhibition factor (MIF), initiates a signaling cascade that contributes to tumor progression. This pathway induces NF-kappa B activation, resulting in the secretion of IL-8 which, in turn, promotes cell survival. Inhibition of this pathway leads to decreased cell survival. These findings could form the basis of unique therapeutic strategies aimed at blocking the CD74-induced, IL-8- dependent survival pathway.