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使用无标记定量蛋白质组学的中空纤维培养系统进行比较分泌组分析表明 PARK7 对肺腺癌细胞增殖以及迁移/侵袭的影响。

Comparative secretome analyses using a hollow fiber culture system with label-free quantitative proteomics indicates the influence of PARK7 on cell proliferation and migration/invasion in lung adenocarcinoma.

机构信息

Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

出版信息

J Proteome Res. 2012 Nov 2;11(11):5167-85. doi: 10.1021/pr300362g. Epub 2012 Oct 4.

Abstract

As the leading cause of cancer death worldwide, lung cancer lacks effective diagnosis tools and treatments to prevent its metastasis. Fortunately, secretome has clinical usages as biomarkers and protein drugs. To discover the secretome that influences lung adenocarcinoma metastasis, the hollow fiber culture (HFC) system was used along with label-free proteomics approach to analyze cell secretomes between CL1-0 and CL1-5 cell lines, which exhibit low and high metastatic potentials. Among the 703 proteins quantified, 50 possessed different levels between CL1-0 and CL1-5. PARK7 was a primary focus because of the lack of research involving lung adenocarcinoma. The cell proliferation, migration, and invasion properties of CL1-0, CL1-5, and A549 cells were significantly diminished when the expression of their PARK7 proteins was reduced. Conversely, these functions were promoted when PARK7 was overexpressed in CL1-0. In clinical expression, PARK7 levels within tissue specimens and plasma samples were significantly higher in the cancer group. This represents the first time the HFC system has been used with label-free quantification to discern the elements of metastasis in lung adenocarcinoma cell secretomes. Likewise, PARK7 has never been researched for its role in promoting lung adenocarcinoma progression.

摘要

作为全球癌症死亡的主要原因,肺癌缺乏有效的诊断工具和治疗方法来预防其转移。幸运的是,分泌组具有作为生物标志物和蛋白质药物的临床用途。为了发现影响肺腺癌转移的分泌组,使用中空纤维培养(HFC)系统和无标记蛋白质组学方法来分析具有低和高转移潜力的 CL1-0 和 CL1-5 细胞系之间的细胞分泌组。在定量的 703 种蛋白质中,有 50 种在 CL1-0 和 CL1-5 之间存在不同水平。由于缺乏涉及肺腺癌的研究,PARK7 是一个主要关注点。当 CL1-0、CL1-5 和 A549 细胞的 PARK7 蛋白表达减少时,细胞增殖、迁移和侵袭特性显著降低。相反,当 PARK7 在 CL1-0 中过表达时,这些功能得到促进。在临床表达中,组织标本和血浆样本中的 PARK7 水平在癌症组中显著升高。这是首次使用无标记定量法与 HFC 系统区分肺腺癌细胞分泌组中的转移成分。同样,PARK7 从未因其在促进肺腺癌进展中的作用而被研究过。

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