Peng Wenjing, Zhang Yu, Zhu Rui, Mechref Yehia
Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX.
Electrophoresis. 2017 Sep;38(17):2124-2134. doi: 10.1002/elps.201700027. Epub 2017 Jul 5.
Breast cancer is the leading type of cancer in women. Breast cancer brain metastasis is currently considered an issue of concern among breast cancer patients. Membrane proteins play important roles in breast cancer brain metastasis, involving cell adhesion and penetration of blood-brain barrier. To understand the mechanism of breast cancer brain metastasis, liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed in conjunction with enrichment of membrane proteins to analyze the proteomes from five different breast cancer and a brain cancer cell lines. Quantitative proteomic data of all cell lines were compared with MDA-MB-231BR which is a brain seeking breast cancer cell line, thus representing brain metastasis characteristics. Label-free proteomics of the six cell lines facilitates the identification of 1238 proteins and the quantification of 899 proteins of which more than 70% were membrane proteins. Unsupervised principal component analysis (PCA) of the label-free proteomics data resulted in a distinct clustering of cell lines, suggesting quantitative differences in the expression of several proteins among the different cell lines. Unique protein expressions in 231BR were observed for 28 proteins. The up-regulation of STAU1, AT1B3, NPM1, hnRNP Q, and hnRNP K and the down-regulation of TUBB4B and TUBB5 were noted in 231BR relative to 231 (precursor cell lines from which 231BR is derived). These proteins might contribute to the breast cancer brain metastasis. Ingenuity pathway analysis (IPA) supported the great brain metastatic propensity of 231BR and suggested the importance of the up-regulation of integrin proteins and down-regulation of EPHA2 in brain metastasis.
乳腺癌是女性中最主要的癌症类型。乳腺癌脑转移目前被认为是乳腺癌患者中一个值得关注的问题。膜蛋白在乳腺癌脑转移中发挥着重要作用，涉及细胞黏附以及血脑屏障的穿透。为了了解乳腺癌脑转移的机制，采用液相色谱-串联质谱法（LC-MS/MS）并结合膜蛋白富集技术，对五种不同的乳腺癌细胞系和一种脑癌细胞系的蛋白质组进行分析。将所有细胞系的定量蛋白质组学数据与MDA-MB-231BR（一种具有脑转移倾向的乳腺癌细胞系）进行比较，从而体现脑转移特征。对这六种细胞系进行的无标记蛋白质组学分析有助于鉴定1238种蛋白质，并对899种蛋白质进行定量，其中70%以上为膜蛋白。对无标记蛋白质组学数据进行无监督主成分分析（PCA），结果显示细胞系明显聚类，表明不同细胞系中几种蛋白质的表达存在定量差异。在231BR中观察到28种蛋白质有独特的表达。相对于231（231BR的前体细胞系），在231BR中注意到STAU1、AT1B3、NPM1、hnRNP Q和hnRNP K上调，而TUBB4B和TUBB5下调。这些蛋白质可能有助于乳腺癌脑转移。 Ingenuity通路分析（IPA）支持231BR具有很高的脑转移倾向，并表明整合素蛋白上调和EPHA2下调在脑转移中的重要性。
