Interleukin 32 Expression in Mesothelioma.

IF 2.6 3区 医学 Q3 ONCOLOGY
Takuya Mikamo, Riko Niwa, Yuki Hanamatsu, Tamotsu Takeuchi
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Abstract

Background: Interleukin 32 (IL32) has context-dependent roles in carcinogenesis across cancer types. In this study, we examined IL32 in mesotheliomas.

Methods: IL32 protein expression was evaluated by immunohistochemistry in 56 mesothelioma tissue microarray specimens and by immunoblot analysis in cultured mesothelioma cell lines. The functional roles of IL32 were examined through ectopic expression of IL32β and IL32θ isoforms in D-Meso-Sonobe cells with epithelial-mesenchymal plasticity and through siRNA-mediated IL32 downregulation followed by cell-detachment-induced apoptosis assays in epithelioid mesothelioma cells.

Results: IL32 immunoreactivity was detected in 20 of 56 mesothelioma tissue specimens, including cytoplasmic staining in 20 of 39 epithelioid cases, whereas little or no immunoreactivity was found in 17 sarcomatoid cases. In immunoblot analysis, an IL32 protein band was detected in two cultured epithelioid mesothelioma cell lines (MPM-2 and TCC-Meso-1), but not in sarcomatoid MPM-1 cells. Two IL32 isoforms, IL32β and IL32θ cDNAs, were isolated from MPM-2 cells. Ectopic expression of IL32θ, but not IL32β, inhibited the morphological transition from epithelioid to sarcomatoid features in D-Meso-Sonobe mesothelioma cells with mesothelial-mesenchymal transition plasticity. Conversely, siRNA-mediated downregulation of IL32 increased cell detachment-induced apoptosis in MPM-2 and TCC-Meso-1 epithelioid mesothelioma cells. Moreover, IL32 suppressed expression of secreted protein acidic and rich in cysteine, which is an epithelial-mesenchymal transition-related protein in mesothelioma cells.

Conclusions: These findings indicate that IL32 is expressed in epithelioid mesothelioma and may contribute to mesotheliomagenesis.

白介素32在间皮瘤中的表达。
背景:白细胞介素32 (IL32)在各种癌症类型的癌变中具有环境依赖性作用。在这项研究中,我们检测了间皮瘤中的IL32。方法:采用免疫组化方法检测56例间皮瘤组织芯片标本中IL32蛋白的表达,免疫印迹法检测培养的间皮瘤细胞系中IL32蛋白的表达。通过在具有上皮-间质可塑性的D-Meso-Sonobe细胞中IL32β和IL32θ亚型的异位表达,以及在上皮样间皮瘤细胞中通过sirna介导的IL32下调和细胞脱落诱导的凋亡实验来检测IL32的功能作用。结果:56例间皮瘤组织标本中有20例检测到IL32免疫反应性,其中39例上皮样标本中有20例检测到细胞质染色,17例肉瘤样标本中检测到IL32免疫反应性低或无反应。在免疫印迹分析中,在两种培养的上皮样间皮瘤细胞系(MPM-2和TCC-Meso-1)中检测到IL32蛋白带,但在肉瘤样MPM-1细胞中未检测到。从MPM-2细胞中分离到两个IL32亚型,IL32β和IL32θ。异位表达IL32θ而非IL32β抑制了D-Meso-Sonobe间皮瘤细胞从上皮样向肉瘤样的形态转变,具有间皮质-间质过渡的可塑性。相反,sirna介导的IL32下调会增加MPM-2和TCC-Meso-1上皮样间皮瘤细胞脱离诱导的凋亡。此外,IL32抑制了间皮瘤细胞分泌的富含半胱氨酸的酸性蛋白的表达,该蛋白是一种上皮-间充质过渡相关蛋白。结论:这些发现表明IL32在上皮样间皮瘤中表达,并可能参与间皮瘤的形成。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Thoracic Cancer
Thoracic Cancer ONCOLOGY-RESPIRATORY SYSTEM
CiteScore
5.20
自引率
3.40%
发文量
439
审稿时长
2 months
期刊介绍: Thoracic Cancer aims to facilitate international collaboration and exchange of comprehensive and cutting-edge information on basic, translational, and applied clinical research in lung cancer, esophageal cancer, mediastinal cancer, breast cancer and other thoracic malignancies. Prevention, treatment and research relevant to Asia-Pacific is a focus area, but submissions from all regions are welcomed. The editors encourage contributions relevant to prevention, general thoracic surgery, medical oncology, radiology, radiation medicine, pathology, basic cancer research, as well as epidemiological and translational studies in thoracic cancer. Thoracic Cancer is the official publication of the Chinese Society of Lung Cancer, International Chinese Society of Thoracic Surgery and is endorsed by the Korean Association for the Study of Lung Cancer and the Hong Kong Cancer Therapy Society. The Journal publishes a range of article types including: Editorials, Invited Reviews, Mini Reviews, Original Articles, Clinical Guidelines, Technological Notes, Imaging in thoracic cancer, Meeting Reports, Case Reports, Letters to the Editor, Commentaries, and Brief Reports.
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