CD30-induced signaling is absent in Hodgkin's cells but present in anaplastic large cell lymphoma cells
CD30-induced signaling is absent in Hodgkin's cells but present in anaplastic large cell lymphoma cells
复制标题
DOI：
10.2353/ajpath.2008.070858
复制
发表时间：
2008-02-01
影响因子：
6
通讯作者：
Duerkop, Horst
中科院分区：
文献类型：
--
作者：
Hirsch, Burkhard;Hummel, Michael;Duerkop, Horst
CD30在经典霍奇金淋巴瘤和间变性大细胞淋巴瘤中高表达。（ALCL）提示该细胞因子受体具有重要的致病作用。为了验证这一假设，我们通过不同的方法研究了霍奇金和ALCL细胞系中的CD30信号：1)CD30刺激，2)CD30下调，以及3)两者结合。在RNA（微阵列和实时定量RT-PCR）、蛋白质（电泳迁移率转移分析、免疫印迹和流式细胞术）和细胞/功能（增殖和凋亡）水平上确定了效果。我们证明霍奇金细胞实际上对CD30没有反应。CD30刺激和CD30沉默对霍奇金细胞均无显著影响。相比之下，CD30刺激ALCL细胞激活核转录因子κ B (nf - κ B)，诱导主要转录变化，并降低增殖。这些作用可以通过下调CD30来消除。在ALCL细胞中，稳定转染显性阴性NF-kappa B抑制剂刺激CD30，可诱导显著的caspase激活和大量凋亡。我们的数据表明，1)CD30信号在霍奇金细胞系中无效，但在ALCL细胞系中有效；2)CD30可能没有显著参与经典霍奇金淋巴瘤的发病机制；3)CD30刺激在ALCL细胞中触发两种相互竞争的效应，即半胱天冬酶的激活和nf - κ b介导的存活。这些数据表明，ALCL的cd30靶向治疗应联合nf - κ B抑制剂诱导有效。
High CD30 expression in classical Hodgkin's lymphoma and anaplastic large cell lymphoma. (ALCL) suggests an important pathogenic role of this cytokine receptor. To test this hypothesis, we investigated CD30 signaling in Hodgkin's and ALCL cell lines by different approaches: 1) CD30 stimulation, 2) CD30 down-regulation, and 3) a combination of both. The effects were determined at the RNA (microarray and real-time quantitative RT-PCR), protein (electrophoretic mobility shift analysis, immunoblot, and flow cytometry), and cellular/functional (proliferation and apoptosis) levels. We demonstrate that Hodgkin's cells are virtually CD30 unresponsive. Neither CD30 stimulation nor CD30 silencing of Hodgkin's cells had any significant effect. In contrast, CD30 stimulation of ALCL cells activated nuclear transcription factor-kappa B (NF-kappa B), induced major transcriptional changes, and decreased proliferation. These effects could be abrogated by down-regulation of CD30. Stimulation of CD30 in ALCL cells, stably transfected with a dominant-negative NF-kappa B inhibitor, induced pronounced caspase activation and massive apoptosis. Our data indicate that 1) CD30 signaling is not effective in Hodgkin's cell lines but is effective in ALCL cell lines, 2) CD30 is probably not significantly involved in the pathogenesis of classical Hodgkin's lymphoma, and 3) CD30 stimulation triggers two competing effects in ALCL cells, namely activation of caspases and NF-kappa B-mediated survival. These data suggest that CD30-targeted therapy in ALCL should be combined with NF-kappa B inhibitors to induce effective.