Osteopontin is a multi-faceted pro-tumorigenic driver for central nervous system lymphoma.
Osteopontin is a multi-faceted pro-tumorigenic driver for central nervous system lymphoma.
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DOI：
10.18632/oncotarget.8537
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发表时间：
2016-05-31
期刊：
影响因子：
--
通讯作者：
Tun HW
中科院分区：
文献类型：
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作者：
Yushi Q;Li Z;Von Roemeling CA;Doeppler H;Marlow LA;Kim BY;Radisky DC;Storz P;Copland JA;Tun HW
与非中枢神经系统弥漫性大B细胞淋巴瘤（DLBCL）相比，骨桥蛋白（OPN）是原发性中枢神经系统淋巴瘤（PCNSL）中表达上调最多的基因。我们在这里表明，OPN是中枢神经系统淋巴瘤脑内肿瘤生长、侵袭和传播的关键介质，这些作用依赖于NF-κB的激活。我们进一步表明，OPN通过一种独特的机制激活NF-κB，其中细胞内OPN （iOPN）导致NF-κB抑制剂A20/TNFAIP3和ABIN1/TNIP1的转录下调，而分泌OPN （sOPN）促进受体介导的NF-κB激活。我们还发现NF-κ b介导的基质金属蛋白酶-8 （MMP-8）的诱导是opn介导的组织侵袭的一个特定特征。这些结果表明，OPN可作为PCNSL患者靶向治疗的候选药物。
Osteopontin (OPN) is the most upregulated gene in primary central nervous system lymphoma (PCNSL) compared to non-CNS diffuse large B cell lymphoma (DLBCL). We show here that OPN is a key mediator of intracerebral tumor growth, invasion, and dissemination in CNS lymphoma, and that these effects depend upon activation of NF-κB. We further show that activation of NF-κB by OPN occurs through a unique mechanism in which intracellular OPN (iOPN) causes transcriptional downregulation of the NF-κB inhibitors, A20/TNFAIP3 and ABIN1/TNIP1, and secretory OPN (sOPN) promotes receptor-mediated activation of NF-κB. We also identify NF-κB-mediated induction of matrix metalloproteinase-8 (MMP-8) as a specific feature of OPN-mediated tissue invasion. These results implicate OPN as a candidate for development of targeted therapy for patients with PCNSL.