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电压门控钾离子通道 Kv1.5 在 B 淋巴细胞生理学中的新作用:与人类淋巴瘤恶性相关的表达。

Emerging role for the voltage-dependent K+ channel Kv1.5 in B-lymphocyte physiology: expression associated with human lymphoma malignancy.

机构信息

3.Universitat de Barcelona, Avda. Diagonal 643, E-08028 Barcelona, Spain.

出版信息

J Leukoc Biol. 2013 Oct;94(4):779-89. doi: 10.1189/jlb.0213094. Epub 2013 Jul 11.

DOI:10.1189/jlb.0213094
PMID:23847097
Abstract

Kv, which play a role in the immune system, are remodeled during carcinogenesis. Leukocytes present a limited Kv repertoire, with Kv1.3 and Kv1.5 as isoforms that are involved in neoplastic processes, such as proliferation and migration. In this study, we identified Kv1.5 in B-lymphocytes, characterized its role in proliferation and migration, and analyzed Kv1.3 and Kv1.5 expression in human non-Hodgkin lymphomas. DLBCL, F, MCL, ALCL, and T, along with control N specimens, were analyzed. Kv1.3 and Kv1.5 were found to be remodeled differentially; whereas Kv1.3 expression did not correlate with the state of dedifferentiation or the nature of lymphomatous cells, Kv1.5 abundance correlated inversely with clinical aggressiveness. Whereas indolent F expressed noticeable levels of Kv1.5, aggressive DLBCL showed low Kv1.5 levels. In addition, control LNs expressed heterogeneous high levels of Kv1.3, which could indicate some reactivity, whereas Kv1.5 abundance was low and quite homogeneous. Our data show that Kv1.5 is a determinant of human B cell proliferation and migration, thereby identifying this channel as a new target for immunomodulation. Our work also provides new insights into the use of Kv1.3 and Kv1.5 as potential targets during tumorigenesis.

摘要

Kv 在免疫系统中发挥作用,在癌变过程中会发生重塑。白细胞呈现有限的 Kv 谱,其中 Kv1.3 和 Kv1.5 是参与肿瘤发生过程(如增殖和迁移)的同工型。在这项研究中,我们鉴定了 B 淋巴细胞中的 Kv1.5,描述了其在增殖和迁移中的作用,并分析了人类非霍奇金淋巴瘤中 Kv1.3 和 Kv1.5 的表达。分析了 DLBCL、F、MCL、ALCL 和 T,以及对照 N 标本。发现 Kv1.3 和 Kv1.5 被差异化重塑;尽管 Kv1.3 的表达与去分化状态或淋巴瘤细胞的性质无关,但 Kv1.5 的丰度与临床侵袭性呈负相关。虽然惰性 F 表达了显著水平的 Kv1.5,但侵袭性 DLBCL 显示出低水平的 Kv1.5。此外,对照 LNs 表达了异构的高水平 Kv1.3,这可能表明存在一些反应性,而 Kv1.5 的丰度较低且相当均匀。我们的数据表明 Kv1.5 是人类 B 细胞增殖和迁移的决定因素,从而将该通道鉴定为免疫调节的新靶标。我们的工作还为 Kv1.3 和 Kv1.5 在肿瘤发生过程中作为潜在靶点的应用提供了新的见解。

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