Autoantibody signatures involving glycolysis and splicesome proteins precede a diagnosis of breast cancer among postmenopausal women.
Autoantibody signatures involving glycolysis and splicesome proteins precede a diagnosis of breast cancer among postmenopausal women.
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DOI：
10.1158/0008-5472.can-12-2560
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发表时间：
2013-03-01
期刊：
影响因子：
11.2
通讯作者：
Hanash S
中科院分区：
文献类型：
--
作者：
Ladd JJ;Chao T;Johnson MM;Qiu J;Chin A;Israel R;Pitteri SJ;Mao J;Wu M;Amon LM;McIntosh M;Li C;Prentice R;Disis N;Hanash S
我们评估了设计用于发展乳腺癌的小鼠模型的自身抗体库，以及在临床前时间点和乳腺癌临床诊断时收集的血浆中的自身抗体库。在寻求识别与体液反应相关的常见途径、网络和蛋白质家族的过程中，我们阐明了肿瘤抗原和自身抗体相互作用的动态性质。将来自 MMTV-neu 小鼠模型和 MCF7 人乳腺癌的永生化细胞系的裂解物蛋白点样到硝酸纤维素微阵列上，并分别与小鼠和人血浆样品杂交。针对糖酵解和剪接体蛋白的基于 Ig 的血浆免疫反应是在荷瘤小鼠和诊断前人类样本中观察到的主要特征。有趣的是，距诊断较远的地方自身抗体反应性比距诊断较近的地方更明显。我们提供了自身抗体反应性随肿瘤发生和进展动态变化的证据，这可能部分取决于抗原抗体相互作用的程度。
We assessed the autoantibody repertoire of a mouse model engineered to develop breast cancer and the repertoire of autoantibodies in plasmas collected at a pre-clinical time point and at the time of clinical diagnosis of breast cancer. In seeking to identify common pathways, networks and protein families associated with the humoral response, we elucidated the dynamic nature of tumor antigens and autoantibody interactions. Lysate proteins from an immortalized cell line from an MMTV-neu mouse model and from MCF7 human breast cancers were spotted onto nitrocellulose microarrays and hybridized with mouse and human plasma samples, respectively. Ig-based plasma immunoreactivity against glycolysis and spliceosome proteins was a predominant feature observed both in tumor bearing mice and in pre-diagnostic human samples. Interestingly, autoantibody reactivity was more pronounced further away than closer to diagnosis. We provide evidence for dynamic changes in autoantibody reactivity with tumor development and progression that may depend in part on the extent of antigen-antibody interactions.