Induction of autotaxin by the Epstein-Barr virus promotes the growth and survival of Hodgkin lymphoma cells
Induction of autotaxin by the Epstein-Barr virus promotes the growth and survival of Hodgkin lymphoma cells
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DOI：
10.1182/blood-2005-02-0471
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发表时间：
2005-09-15
期刊：
影响因子：
20.3
通讯作者：
Murray, PG
中科院分区：
文献类型：
--
作者：
Baumforth, KRN;Flavell, JR;Murray, PG
一部分霍奇金淋巴瘤患者在其肿瘤细胞中携带EB病毒（EBV），一种致癌疱疹病毒。虽然人们普遍认为EBV导致霍奇金淋巴瘤细胞的恶性表型，但缺乏支持这一观点的直接证据。在这里，我们表明，EB病毒感染霍奇金淋巴瘤细胞的诱导自分泌运动因子，分泌的肿瘤相关因子与溶血磷脂酶D活性的结果。自分泌运动因子的上调增加了溶血磷脂酸（LPA）的产生，并导致霍奇金淋巴瘤细胞的生长和存活增强，而自分泌运动因子的特异性下调降低了LPA水平，并降低了细胞的生长和活力。在淋巴瘤组织中，自分泌运动因子的表达主要局限于CD 30（+）间变性大细胞淋巴瘤和霍奇金淋巴瘤;在后者中，高水平的自分泌运动因子与EBV阳性密切相关（P = 0.006）。我们的研究结果确定了自分泌运动因子的诱导和随后产生的LPA作为介导EBV诱导的霍奇金淋巴瘤细胞生长和存活的关键分子事件，并表明该途径可能为新的治疗干预提供机会。
A proportion of patients with Hodgkin lymphoma carry Epstein-Barr virus (EBV), an oncogenic herpesvirus, in their tumor cells. Although it is generally assumed that EBV contributes to the malignant phenotype of Hodgkin lymphoma cells, direct evidence in support of this is lacking. Here we show that EBV infection of Hodgkin lymphoma cells results in the induction of autotaxin, a secreted tumor-associated factor with lysophospholipase-D activity. Up-regulation of autotaxin increased the generation of lysophosphatidic acid (LPA) and led to the enhanced growth and survival of Hodgkin lymphoma cells, whereas specific down-regulation of autotaxin decreased LPA levels and reduced cell growth and viability. In lymphoma tissues, autotaxin expression was mainly restricted to CD30(+) anaplastic large-cell lymphomas and Hodgkin lymphoma; in the latter, high levels of autotaxin were strongly associated with EBV positivity (P =.006). Our results identify the induction of autotaxin and the subsequent generation of LPA as key molecular events that mediate the EBV-induced growth and survival of Hodgkin lymphoma cells and suggest that this pathway may provide opportunities for novel therapeutic intervention.