STAT3 is constitutively activated in Hodgkin cell lines
STAT3 is constitutively activated in Hodgkin cell lines
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DOI：
10.1182/blood.v98.3.762
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发表时间：
2001-08-01
期刊：
影响因子：
20.3
通讯作者：
Tesch, H
中科院分区：
文献类型：
--
作者：
Kube, D;Holtick, U;Tesch, H
何杰金氏病（HD）是一种恶性淋巴瘤，其中假定的恶性何杰金氏和里德-斯滕伯格细胞是罕见的，并被大量的反应性非恶性细胞包围。研究表明，细胞因子如白细胞介素-6（IL-6）参与了该病的发病机制。研究了HD细胞系中IL-6受体（IL-6 R）复合物的表达及其与信号转导和转录激活因子（STAT）分子激活的联系。凝胶阻滞和Western印迹分析显示，在7个HD细胞系中的5个中存在高水平的组成性激活的STAT 3，这在Burkitt淋巴瘤细胞系中无法检测到。在各种HD细胞系中测量了不同水平的IL-6 R蛋白：L428和Dev细胞的特征在于非常低水平的gp 80和gp 130，在KMH 2细胞上仅检测到gp 130但未检测到gp 80，而L540、L591、HDLM 2和L1236对gp 80和gp 130均呈阳性，表明可能存在STAT 3的自分泌刺激。然而，没有观察到IL-6或IL-6/可溶性IL-6 R刺激时STAT 3活化的进一步增加。针对IL-6、gp 80、gp 130或这两种受体亚基的中和单克隆抗体不影响HD细胞系中STAT分子的增殖或组成性激活。然而，酪氨酸激酶抑制剂AG 490阻断了STAT 3的组成性激活并抑制了HD肿瘤细胞的自发生长。证据表明，异常STAT信号和生长调节霍奇金细胞系。(C)2001年，美国血液学会。
Hodgkin disease (HD) represents a malignant lymphoma in which the putative malignant Hodgkin and Reed-Sternberg cells are rare and surrounded by abundant reactive nonmalignant cells. It has been suggested that cytokines such as interleukin-6 (IL-6) are involved in the pathogenesis of the disease. The expression of the IL-6 receptor (IL-6R) complex and its link to the activation of signal transducers and activators of transcription (STAT) molecules in HD cell lines was investigated. Gel retardation and Western blot analyses revealed a high level of constitutively activated STAT3 in 5 of 7 HD cell lines, which could not be detected in Burkitt lymphoma cell lines. Different levels of IL-6R protein were measured in various HD cell lines: L428 and Dev cells were characterized by very low levels of gp80 and gp130, on KMH2 cells only gp130 but no gp80 was detected, whereas L540, L591, HDLM2, and L1236 were positive for both gp80 and gp130, suggesting a possible autocrine stimulation of STAT3. However, a further increase in STAT3 activation on IL-6 or IL-6/soluble IL-6R stimulation was not observed. Neutralizing monoclonal antibodies against IL-6, gp80, gp130, or both receptor subunits did not affect the proliferation or the constitutive activation of STAT molecules in HD cell lines. However, the tyrosine kinase Inhibitor AG490 blocked the constitutive activation of STAT3 and inhibited spontaneous growth of HD tumor cells. The evidence suggests abnormal STAT signaling and growth regulation in Hodgkin cell lines. (C) 2001 by The American Society of Hematology.