The matrisome: in silico definition and in vivo characterization by proteomics of normal and tumor extracellular matrices.
The matrisome: in silico definition and in vivo characterization by proteomics of normal and tumor extracellular matrices.
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DOI：
10.1074/mcp.m111.014647
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发表时间：
2012-04
期刊：
影响因子：
--
通讯作者：
Hynes RO
中科院分区：
文献类型：
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作者：
Naba A;Clauser KR;Hoersch S;Liu H;Carr SA;Hynes RO
细胞外基质（ECM）是一个复杂的交联蛋白质网络，提供生物物理和生物化学线索，是细胞增殖，存活，分化和迁移的重要调节因子。在这里，我们提出了一种蛋白质组学策略，开发的特点在体内的ECM组成的正常组织和肿瘤使用富集的蛋白质提取物的ECM成分和随后的质谱分析。与此同时，我们已经开发了一种生物信息学方法来预测计算机“基质体”定义为ECM蛋白和相关因子的集合。我们报告了小鼠肺和结肠的细胞外基质的表征，每个细胞外基质包含100多种ECM蛋白，每个蛋白都呈现出特征性的特征。此外，使用人肿瘤异种移植物在小鼠中，我们表明，肿瘤细胞和基质细胞都有助于肿瘤基质的产生，并且不同转移潜能的肿瘤在肿瘤和基质来源的ECM组分中不同。我们在这里描述和说明的策略可以广泛应用，并促进其他人应用这些方法，我们提供的资源，包括实验室协议，ECM域和蛋白质的库存，以及用于生物信息学推导人类和小鼠基质体的说明。
The extracellular matrix (ECM) is a complex meshwork of cross-linked proteins providing both biophysical and biochemical cues that are important regulators of cell proliferation, survival, differentiation, and migration. We present here a proteomic strategy developed to characterize the in vivo ECM composition of normal tissues and tumors using enrichment of protein extracts for ECM components and subsequent analysis by mass spectrometry. In parallel, we have developed a bioinformatic approach to predict the in silico “matrisome” defined as the ensemble of ECM proteins and associated factors. We report the characterization of the extracellular matrices of murine lung and colon, each comprising more than 100 ECM proteins and each presenting a characteristic signature. Moreover, using human tumor xenografts in mice, we show that both tumor cells and stromal cells contribute to the production of the tumor matrix and that tumors of differing metastatic potential differ in both the tumor- and the stroma-derived ECM components. The strategy we describe and illustrate here can be broadly applied and, to facilitate application of these methods by others, we provide resources including laboratory protocols, inventories of ECM domains and proteins, and instructions for bioinformatically deriving the human and mouse matrisome.