Department of Proteomics and Signal Transduction, Max-Planck-Institute of Biochemistry, Martinsried, Germany.
Mol Syst Biol. 2012;8:611. doi: 10.1038/msb.2012.44.
We report a proteomic analysis of microdissected material from formalin-fixed and paraffin-embedded colorectal cancer, quantifying > 7500 proteins between patient matched normal mucosa, primary carcinoma, and nodal metastases. Expression levels of 1808 proteins changed significantly between normal and cancer tissues, a much larger fraction than that reported in transcript-based studies. Tumor cells exhibit extensive alterations in the cell-surface and nuclear proteomes. Functionally similar changes in the proteome were observed comparing rapidly growing and differentiated CaCo-2 cells. In contrast, there was minimal proteomic remodeling between primary cancer and metastases, suggesting that no drastic proteome changes are necessary for the tumor to propagate in a different tissue context. Additionally, we introduce a new way to determine protein copy numbers per cell without protein standards. Copy numbers estimated in enterocytes and cancer cells are in good agreement with CaCo-2 and HeLa cells and with the literature data. Our proteomic data set furthermore allows mapping quantitative changes of functional protein classes, enabling novel insights into the biology of colon cancer.
我们报告了一项对福尔马林固定和石蜡包埋的结直肠癌进行微切割的蛋白质组学分析，定量了超过 7500 种蛋白质，这些蛋白质存在于患者匹配的正常黏膜、原发性癌和淋巴结转移之间。在正常组织和癌症组织之间，1808 种蛋白质的表达水平发生了显著变化，这一比例远远高于基于转录本的研究报告的比例。肿瘤细胞的细胞表面和核蛋白质组发生了广泛的改变。比较快速生长和分化的 CaCo-2 细胞，观察到功能相似的蛋白质组变化。相比之下，原发性癌症和转移之间的蛋白质组重塑最小，这表明肿瘤在不同的组织环境中传播不需要剧烈的蛋白质组变化。此外，我们引入了一种新的方法，无需蛋白质标准即可确定每个细胞的蛋白质拷贝数。在肠细胞和癌细胞中估计的拷贝数与 CaCo-2 和 HeLa 细胞以及文献数据相符。我们的蛋白质组数据集还允许对功能蛋白质类别的定量变化进行映射，从而为结肠癌的生物学提供新的见解。
