MALDI Mass Spectrometry Imaging of N-Linked Glycans in Cancer Tissues.
MALDI Mass Spectrometry Imaging of N-Linked Glycans in Cancer Tissues.
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癌组织中N连锁聚糖的MALDI质谱成像。
DOI：
10.1016/bs.acr.2016.11.009
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发表时间：
2017
影响因子：
--
通讯作者：
Angel PM
中科院分区：
文献类型：
--
作者：
Drake RR;Powers TW;Jones EE;Bruner E;Mehta AS;Angel PM
糖基化蛋白占细胞表面、分泌和循环蛋白翻译后修饰的大部分。在肿瘤微环境中，免疫细胞、细胞外基质蛋白、细胞表面受体的存在以及基质与肿瘤细胞之间的相互作用都是由糖链结合和识别反应介导的过程。肿瘤发生过程中糖基化的变化是有充分证据证明的，并影响所有这些相关的黏附和调节功能。最近开发了一种MALDI成像质谱仪(MALDI-IMS)工作流程，用于分析新鲜/冷冻组织和福尔马林固定石蜡包埋(FFPE)组织中N-连接的糖链分布。这种方法的关键是将多肽-N-糖苷酶的分子涂层应用于组织，这种酶可以将天冬酰胺连接的多糖从蛋白质载体上分解出来。然后可以用MALDI-IMS直接在组织上分析释放的N-连接的葡聚糖。通常情况下，常规检测到40个或更多的单个糖链结构，当结合组织病理学定位时，相对于非肿瘤区域和其他结构特征，肿瘤特异性糖链很容易分组。这项技术是糖生物学和质谱学成像研究方法学的最新发展和新方法，因此讨论了潜在的用途，如肿瘤特异性的糖链生物标志物面板和其他应用。
Glycosylated proteins account for a majority of the post-translation modifications of cell surface, secreted and circulating proteins. Within the tumor microenvironment, the presence of immune cells, extracellular matrix proteins, cell surface receptors and interactions between stroma and tumor cells are all processes mediated by glycan binding and recognition reactions. Changes in glycosylation during tumorigenesis are well documented to occur, and affect all of these associated adhesion and regulatory functions. A MALDI imaging mass spectrometry (MALDI-IMS) workflow for profiling N-linked glycan distributions in fresh/frozen tissues and formalin-fixed paraffin-embedded (FFPE) tissues has recently been developed. The key to the approach is the application of a molecular coating of peptide-N-glycosidase to tissues, an enzyme that cleaves asparagine-linked glycans from their protein carrier. The released N-linked glycans can then be analyzed by MALDI-IMS directly on tissue. Generally 40 or more individual glycan structures are routinely detected, and when combined with histopathology localizations, tumor specific glycans are readily grouped relative to non-tumor regions and other structural features. This technique is a recent development and new approach in glycobiology and mass spectrometry imaging research methodology, thus potential uses such as tumor-specific glycan biomarker panels and other applications are discussed.
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