Inferring alterations in cell-to-cell communication in HER2+ breast cancer using secretome profiling of three cell models.
Inferring alterations in cell-to-cell communication in HER2+ breast cancer using secretome profiling of three cell models.
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DOI：
10.1002/bit.25238
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发表时间：
2014-09
影响因子：
3.8
通讯作者：
Byrne-Hoffman, Christina
中科院分区：
文献类型：
--
作者：
Klinke, David J., II;Kulkarni, Yogesh M.;Wu, Yueting;Byrne-Hoffman, Christina
关键词：
在证明对分子靶向治疗的持久临床反应方面的挑战引发了将癌症视为进化过程的重新出现。在体细胞进化中，细胞变体通过体细胞突变的随机过程引入，并通过生存竞争选择以改善适应性。与达尔文进化论相反，保留下来的细胞变异可能直接改变适应性竞争。如果细胞与细胞之间的交流对选择很重要，那么恶性细胞分泌的生化信号应该被改变，以使这种适应性竞争产生偏差。为了验证这一假设，我们使用利用二维凝胶电泳（2DE）和MALDI-TOF质谱的蛋白质组学工作流程，比较了两种人HER 2+乳腺癌细胞系（BT474和SKBR 3）相对于正常人乳腺上皮细胞系（184 A1）体外分泌的蛋白质。支持的2DE分泌组图谱和鉴定的蛋白质，这两个乳腺癌细胞系表现出分泌组的配置文件，是彼此相似的，但不同的184 A1分泌组。使用蛋白质-蛋白质相互作用和途径推断工具进行功能注释，结果表明所有三种细胞系都分泌外泌体，如扫描电子显微镜所证实的。有趣的是，HER 2+乳腺癌细胞系外泌体富含参与抗原加工和呈递以及糖酵解代谢的蛋白质。这些途径与癌症的两个新出现的标志有关：逃避肿瘤免疫监视和解除细胞能量调节。
Challenges in demonstrating durable clinical responses to molecular-targeted therapies has sparked a re-emergence in viewing cancer as an evolutionary process. In somatic evolution, cellular variants are introduced through a random process of somatic mutation and are selected for improved fitness through a competition for survival. In contrast to Darwinian evolution, cellular variants that are retained may directly alter the fitness competition. If cell-to-cell communication is important for selection, the biochemical cues secreted by malignant cells that emerge should be altered to bias this fitness competition. To test this hypothesis, we compared the proteins secreted in vitro by two human HER2+ breast cancer cell lines (BT474 and SKBR3) relative to a normal human mammary epithelial cell line (184A1) using a proteomics workflow that leveraged two-dimensional gel electrophoresis (2DE) and MALDI-TOF mass spectrometry. Supported by the 2DE secretome maps and identified proteins, the two breast cancer cell lines exhibited secretome profiles that were similar to each other and, yet, were distinct from the 184A1 secretome. Using protein-protein interaction and pathway inference tools for functional annotation, the results suggest that all three cell lines secrete exosomes, as confirmed by scanning electron microscopy. Interestingly, the HER2+ breast cancer cell line exosomes are enriched in proteins involved in antigen processing and presentation and glycolytic metabolism. These pathways are associated with two of the emerging hallmarks of cancer: evasion of tumor immunosurveillance and deregulating cellular energetics.
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影响因子：
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