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IL-13 和 IL-13Rα1 在结外自然杀伤/T 细胞淋巴瘤中过表达,并介导肿瘤细胞增殖。

IL-13 and IL-13Rα1 are overexpressed in extranodal natural killer/T cell lymphoma and mediate tumor cell proliferation.

机构信息

Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People's Republic of China.

Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People's Republic of China.

出版信息

Biochem Biophys Res Commun. 2018 Sep 18;503(4):2715-2720. doi: 10.1016/j.bbrc.2018.08.030. Epub 2018 Aug 11.

DOI:10.1016/j.bbrc.2018.08.030
PMID:30107911
Abstract

Extranodal NK/T cell lymphoma (NKTCL) is a rare but aggressive subtype of non-Hodgkin lymphoma. Multi-agent chemotherapy and involved-field radiotherapy are used to treat this disease, but the prognosis remains poor. Interleukin 13 and its receptors (IL-13Rs) are correlated with the pathogenesis and progression of various malignances. However, their roles in NKTCL have not been evaluated. In this study, we examined the roles of IL-13 and IL-13Rs in NKTCL and the underlying mechanisms. We found significantly higher serum IL-13 levels (p < 0.001) and IL-13Rα1 expression in tumor tissues (36 of 40, p < 0.001) in patients with NKTCL than in control cohort. IL-13 secretion was observed in tumor tissues (30 of 40, p < 0.001) and several cell lines of NKTCL. However, we did not detect significant associations between clinical characteristics and the expression levels of IL-13 or IL-13Rs. In vitro, IL-13 activated Stat6 and promoted cell proliferation in a dose-dependent manner. In addition, blocking IL-13 exerted a negative effect on tumor cell growth. We conclude that IL-13 functions as an autocrine growth factor in NKTCL and contributes to its pathogenesis. Blocking IL-13 is thus a potential therapeutic approach for NKTCL.

摘要

结外 NK/T 细胞淋巴瘤(NKTCL)是一种罕见但侵袭性较强的非霍奇金淋巴瘤亚型。多药化疗和累及野放疗用于治疗这种疾病,但预后仍然较差。白细胞介素 13 及其受体(IL-13Rs)与各种恶性肿瘤的发病机制和进展相关。然而,它们在 NKTCL 中的作用尚未得到评估。在这项研究中,我们研究了 IL-13 和 IL-13Rs 在 NKTCL 中的作用及其潜在机制。我们发现 NKTCL 患者的血清 IL-13 水平(p<0.001)和肿瘤组织中 IL-13Rα1 表达(40 例中有 36 例,p<0.001)显著高于对照组。在肿瘤组织(40 例中有 30 例,p<0.001)和几种 NKTCL 细胞系中观察到 IL-13 的分泌。然而,我们没有发现 IL-13 或 IL-13Rs 的表达水平与临床特征之间存在显著相关性。在体外,IL-13 以剂量依赖的方式激活 Stat6 并促进细胞增殖。此外,阻断 IL-13 对肿瘤细胞生长产生负面影响。我们得出结论,IL-13 在 NKTCL 中作为自分泌生长因子发挥作用,有助于其发病机制。因此,阻断 IL-13 可能是 NKTCL 的一种潜在治疗方法。

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