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Quantitative proteomic analysis of murine white adipose tissue for peritoneal cancer metastasis
Analytical and Bioanalytical Chemistry ( IF 3.8 ) Pub Date : 2017-12-27 , DOI: 10.1007/s00216-017-0813-9
Peter E. Feist , Elizabeth A. Loughran , M. Sharon Stack , Amanda B. Hummon

Cancer metastasis risk increases in older individuals, but the mechanisms for this risk increase are unclear. Many peritoneal cancers, including ovarian cancer, preferentially metastasize to peritoneal fat depots. However, there is a dearth of studies exploring aged peritoneal adipose tissue in the context of cancer. Because adipose tissue produces signals which influence several diseases including cancer, proteomics of adipose tissue in aged and young mice may provide insight into metastatic mechanisms. We analyzed mesenteric, omental, and uterine adipose tissue groups from the peritoneal cavities of young and aged C57BL/6J mouse cohorts with a low-fraction SDS-PAGE gelLC-MS/MS method. We identified 2308 protein groups and quantified 2167 groups, among which several protein groups showed twofold or greater abundance differences between the aged and young cohorts. Cancer-related gene products previously identified as significant in another age-related study were found altered in this study. Several gene products known to suppress proliferation and cellular invasion were found downregulated in the aged cohort, including R-Ras, Arid1a, and heat shock protein β1. In addition, multiple protein groups were identified within single cohorts, including the proteins Cd11a, Stat3, and Ptk2b. These data suggest that adipose tissue is a strong candidate for analysis to identify possible contributors to cancer metastasis in older subjects. The results of this study, the first of its kind using uterine adipose tissue, contribute to the understanding of the role of adipose tissue in age-related alteration of oncogenic pathways, which may help elucidate the mechanisms of increased metastatic tumor burden in the aged.

Open image in new windowGraphical abstract
Graphical abstract

We analyzed mesenteric, omental, and uterine adipose tissue groups from the peritoneal cavities of young and aged C57BL/6J mouse cohorts with a low-fraction SDS-PAGE gelLC-MS/MS method. These fat depots are preferential sites for many peritoneal cancers. The results of this study, the first of its kind using uterine adipose tissue, contribute to the understanding of the role of adipose tissue in age-related alteration of oncogenic pathways, which may help elucidate the mechanisms of increased metastatic tumor burden in the aged.



中文翻译:

小鼠白色脂肪组织对腹膜癌转移的定量蛋白质组学分析

老年人的癌症转移风险增加,但这种风险增加的机制尚不清楚。许多腹膜癌,包括卵巢癌,优先转移至腹膜脂肪库。然而,缺乏在癌症背景下探索老化的腹膜脂肪组织的研究。由于脂肪组织会产生影响包括癌症在内的多种疾病的信号,因此老年和幼年小鼠脂肪组织的蛋白质组学可能会提供有关转移机制的见解。我们使用低分数SDS-PAGE gelLC-MS / MS方法分析了年轻和老年C57BL / 6J小鼠队列腹膜腔的肠系膜,网膜和子宫脂肪组织。我们确定了2308个蛋白质组并量化了2167个组,其中几个蛋白质组在老年人和年轻人中显示出两倍或更大的丰度差异。先前在另一项与年龄相关的研究中被认为具有重要意义的癌症相关基因产物在该研究中被发现发生了改变。在老年队列中发现了几种抑制增殖和细胞侵袭的基因产物,包括R-Ras,Arid1a和热休克蛋白β1,它们被下调。此外,在单个队列中鉴定了多个蛋白质组,包括蛋白质Cd11a,Stat3和Ptk2b。这些数据表明,脂肪组织是分析以确定老年受试者癌症转移的可能因素的有力候选者。该研究的结果是首次使用子宫脂肪组织进行的研究,

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图形概要

我们使用低分数SDS-PAGE gelLC-MS / MS方法分析了年轻和老年C57BL / 6J小鼠队列腹膜腔的肠系膜,网膜和子宫脂肪组织。这些脂肪库是许多腹膜癌的优先部位。这项研究的结果是首次使用子宫脂肪组织进行的研究,有助于了解脂肪组织在与年龄相关的致癌途径改变中的作用,这可能有助于阐明老年人转移性肿瘤负担增加的机制。

更新日期:2017-12-27
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