Quantitative secretomic analysis of pancreatic cancer cells in serum-containing conditioned medium.

Quantitative secretomic analysis of pancreatic cancer cells in serum-containing conditioned medium.
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DOI:
10.1038/srep37606
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发表时间:
2016-11-21
期刊:
影响因子:
4.6
通讯作者:
Zhang Y
Zhang Y
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Liu P;Weng Y;Sui Z;Wu Y;Meng X;Wu M;Jin H;Tan X;Zhang L;Zhang Y

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胰腺癌是一种高度转移和化疗耐药的疾病。参与细胞间相互作用的分泌蛋白在改变肿瘤微环境中发挥着重要作用。由于胎牛血清(FBS)的严重干扰,以往的研究一般集中于无血清培养基中癌细胞系的分泌组。然而,血清饥饿可能会改变分泌蛋白的表达模式。因此,在含血清培养基的蛋白质组学分析中减少血清干扰的努力受到了定量测量肿瘤分泌水平的阻碍。最近,代谢标记、蛋白质均衡、蛋白质分级和过滤辅助样品制备(FASP)策略(MLEFF)已成功用于避免血清对分泌组分析的干扰。在这里,这种有效的方法被应用于两种具有差异转移潜力的仓鼠胰腺癌细胞的比较分泌组分析,从而能够观察到161个差异表达的蛋白质,其中包括先前报道并在血浆中检测到的106个蛋白质。通过对我们的数据和公开的生物信息学资源的综合分析,我们发现由 CDH3、PLAU 和 LFNG 组成的组合面板可能会改善胰腺癌总体生存的预后。这些分泌蛋白可能作为胰腺癌转移的潜在治疗靶点。
Pancreatic cancer is a highly metastatic and chemo-resistant disease. Secreted proteins involved in cell-cell interactions play an important role in changing the tumor microenvironment. Previous studies generally focus on the secretome of cancer cell line from serum-free media, due to the serious interference of fetal bovine serum (FBS). However, serum-starvation may alter expression patterns of secreted proteins. Hence, efforts to decrease the interference of serum in proteomic analysis of serum-containing media have been hampered to quantitatively measure the tumor secretion levels. Recently, the metabolic labeling, protein equalization, protein fractionation and filter-aided sample preparation (FASP) strategy (MLEFF) has been successfully used to avoid the disturbance of serum on secretome analysis. Here, this efficient method was applied for comparative secretome analysis of two hamster pancreatic cancer cells with differentially metastatic potentials, enabling the observation of 161 differentially expressed proteins, including 106 proteins that had been previously reported and detected in plasma. By integrated analysis of our data and publicly available bioinformatics resources, we found that a combination panel consisting of CDH3, PLAU, and LFNG might improve the prognosis of overall pancreatic cancer survival. These secreted proteins may serve as a potential therapeutic targets for pancreatic cancer metastasis.
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