Effect of Lung Squamous Cell Carcinoma Tumor Microenvironment on the CD105(+) Endothelial Cell Proteome
Effect of Lung Squamous Cell Carcinoma Tumor Microenvironment on the CD105(+) Endothelial Cell Proteome
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肺鳞癌肿瘤微环境对CD105( )内皮细胞蛋白质组的影响
DOI：
10.1021/pr5006229
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发表时间：
2014
影响因子：
4.4
通讯作者：
Yongxiang Zhao
中科院分区：
文献类型：
--
作者：
Huiqin Zhuo;Zhi Lyu;Jing Su;Jian He;Yihua Pei;Xiao Cheng;Nuo Zhou;Xiaoling Lu;Sufang Zhou;Yongxiang Zhao
在肺癌中，针对肿瘤内皮细胞（EC）的抗血管生成治疗提供了生存优势。为了充分阐明 ECs 在肿瘤微环境中的行为，通过用抗 CD105 抗体包被的磁珠孵育细胞，从肺鳞状细胞癌中纯化高纯度 (>98%) 正常、肿瘤旁和肿瘤来源的 CD105+ECs。这些细胞表现出典型的 EC 特征。通过同量异位稳定同位素标签和二维 LC/MS/MS (iTRAQ-2DLC/MS/MS) 总共鉴定了 1765 种蛋白质，具有高置信度。特别是，与正常 EC 相比，在肿瘤旁和肿瘤来源的 EC 中分别有 178 和 162 个蛋白质差异表达。上调和下调趋势显示出良好的批间相关性。使用基因本体论，将它们分类为参与细胞代谢过程的主要重编程、氧化应激反应、氧化还原稳态、细胞凋亡和血小板脱颗粒/激活的基因。此外，启动肿瘤血管生成的内皮细胞似乎获得了独特的特性。例如，肿瘤旁来源的 EC 的细胞迁移和平滑肌细胞迁移的调节明显快于正常和肿瘤来源的 EC。其中，两种迁移相关蛋白，神经毡蛋白1和血小板衍生生长因子受体β，主要表达于16名肺鳞状细胞癌患者的癌旁EC中，被确定为抗血管生成治疗的潜在生物标志物。
In lung cancer, antiangiogenic treatment targeting tumor endothelial cells (ECs) provides a survival advantage. To fully elucidate the behavior of ECs in a tumor microenvironment, high-purity (>98%) normal, paratumor-, and tumor-derived CD105+ECs were purified from lung squamous cell carcinoma by incubating cells with anti-CD105 antibody-coated magnetic beads. These cells exhibited typical EC characteristics. Totally, 1765 proteins were identified with high confidence by isobaric stable isotope tags and two-dimensional LC/MS/MS (iTRAQ-2DLC/MS/MS). In particular, 178 and 162 proteins were differentially expressed in paratumor- and tumor-derived ECs, respectively, compared to normal ECs. The up- and down-regulation trends showed good interassay correlation. Using gene ontology, they were classified into genes involved in major reprogramming of cellular metabolic processes, oxidative stress response, redox homeostasis, apoptosis, and platelet degranulation/activation. Moreover, tumor angiogenesis-initiating ECs appeared to acquire distinct properties. For example, cell migration and regulation of smooth muscle cell migration of paratumor-derived ECs were significantly faster than that of normal and tumor-derived ECs. Among them, two migration-associated proteins, neuropilin 1 and platelet-derived growth factor receptor β predominantly expressed in ECs of paratumor from 16 patients with lung squamous cell carcinoma, were identified as potential biomarkers for antiangiogenic therapy.