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骨钙素-2(STC2):一种潜在的肺癌生物标志物,可促进肺癌转移和进展。

Stanniocalcin-2 (STC2): A potential lung cancer biomarker promotes lung cancer metastasis and progression.

作者信息

Na Sang-su, Aldonza Mark Borris, Sung Hye-Jin, Kim Yong-In, Son Yeon Sung, Cho Sukki, Cho Je-Yoel

机构信息

Department of Biochemistry, BK21 PLUS Program for Creative Veterinary Science Research and Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Republic of Korea; Department of Physical Therapy, College of Rehabilitation, Daegu University, Daegu, Republic of Korea.

Department of Biochemistry, BK21 PLUS Program for Creative Veterinary Science Research and Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Republic of Korea.

出版信息

Biochim Biophys Acta. 2015 Jun;1854(6):668-76. doi: 10.1016/j.bbapap.2014.11.002. Epub 2014 Nov 14.

Abstract

The homodimeric glycoprotein, stanniocalcin 2 (STC2) is previously known to be involved in the regulation of calcium and phosphate transport in the kidney and also reported to play multiple roles in several cancers. However, its function and clinical significance in lung cancer have never been reported and still remain uncertain. Here, we investigated the possibility of STC2 as a lung cancer biomarker and identified its potential role in lung cancer cell growth, metastasis and progression. Proteomic analysis of secretome of primary cultured lung cancer cells revealed higher expression of STC2 in cancers compared to that of adjacent normal cells. RT-PCR and Western blot analyses showed higher mRNA and protein expressions of STC2 in lung cancer tissues compared to the adjacent normal tissues. Knockdown of STC2 in H460 lung cancer cells slowed down cell growth progression and colony formation. Further analysis revealed suppression of migration, invasion and delayed G0/G1 cell cycle progression in the STC2 knockdown cells. STC2 knockdown also attenuated the H202-induced oxidative stress on H460 cell viability with a subsequent increase in intracellular ROS levels, which suggest a protective role of STC2 in redox regulatory system of lung cancer. These findings suggest that STC2 can be a potential lung cancer biomarker and plays a positive role in lung cancer metastasis and progression. This article is part of a Special Issue entitled: Medical Proteomics.

摘要

同二聚体糖蛋白——骨钙素2(STC2),此前已知其参与肾脏中钙和磷酸盐转运的调节,并且也有报道称其在多种癌症中发挥多种作用。然而,其在肺癌中的功能和临床意义从未被报道过,仍然不确定。在此,我们研究了STC2作为肺癌生物标志物的可能性,并确定了其在肺癌细胞生长、转移和进展中的潜在作用。对原代培养肺癌细胞分泌组的蛋白质组学分析显示,与相邻正常细胞相比,癌症中STC2的表达更高。逆转录-聚合酶链反应(RT-PCR)和蛋白质印迹分析表明,与相邻正常组织相比,肺癌组织中STC2的mRNA和蛋白质表达更高。在H460肺癌细胞中敲低STC2可减缓细胞生长进程和集落形成。进一步分析显示,STC2敲低的细胞中迁移、侵袭受到抑制,G0/G1细胞周期进程延迟。STC2敲低还减弱了H2O2对H460细胞活力的氧化应激,随后细胞内活性氧水平升高,这表明STC2在肺癌的氧化还原调节系统中具有保护作用。这些发现表明,STC2可能是一种潜在的肺癌生物标志物,并且在肺癌转移和进展中发挥积极作用。本文是名为“医学蛋白质组学”的特刊的一部分。

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