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低氧标记物吡咪唑在乳腺肿瘤模型中的质谱成像

发布时间: 2018-07-04 12:15 来源: 科瑞恩特(北京)科技有限公司
领域: 细胞生物学,微生物,分子生物学,蛋白/抗体/蛋白质组,多组学/蛋白质组/代谢组/脂质组
样品:小鼠乳腺肿瘤组织项目:低氧标记物吡咪唑
参考:Anal. Chem. 2016, 88, 3107−3114, DOI: 10.1021/acs.analchem.5b04032

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低氧标记物吡咪唑在乳腺肿瘤模型中的质谱成像

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Although tumor hypoxia is associated with tumor aggressiveness and resistance to cancer treatment, many details of hypoxia-induced changes in tumors remain to be elucidated. Mass spectrometry imaging (MSI) is a technique that is well suited to study the biomolecular composition of specific tissue regions,such as hypoxic tumor regions. Here, we investigate the use of pimonidazole as an exogenous hypoxia marker for matrix-assisted laser desorption/ionization (MALDI) MSI. In hypoxic cells, pimonidazole is reduced and forms reactive products that bind to thiol groups in proteins, peptides, and amino acids. We show that a reductively activated pimonidazole metabolite can be imaged by MALDI-MSI in a breast tumor xenograft model. Immunohistochemical detection of pimonidazole adducts on adjacent tissue sections confirmed that this metabolite is localized to hypoxic tissue regions. We used this metabolite to image hypoxic tissue regions and their associated lipid and small molecule distributions with MALDI-MSI. We identified a heterogeneous distribution of 1-methylnicotinamide and acetylcarnitine, which mostly colocalized with hypoxic tumor regions. As pimonidazole is a widely used immunohistochemical marker of tissue hypoxia, it is likely that the presented direct MALDI-MSI approach is also applicable to other tissues from pimonidazole-injected animals or humans.

2016 Analytical Chemistry-Mass Spectrometry Imaging of the Hypoxia Marker Pimonidazole ina Breast Tumor Model.jpg

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