Stromal response to prostate cancer: nanotechnology-based detection of thioredoxin-interacting protein partners distinguishes prostate cancer associated stroma from that of benign prostatic hyperplasia.
Stromal response to prostate cancer: nanotechnology-based detection of thioredoxin-interacting protein partners distinguishes prostate cancer associated stroma from that of benign prostatic hyperplasia.
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DOI：
10.1371/journal.pone.0060562
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Smith S
中科院分区：
文献类型：
--
作者：
Singer E;Linehan J;Babilonia G;Imam SA;Smith D;Loera S;Wilson T;Smith S
反应性间质的组织学染色已被证明是前列腺癌生化复发的预测因子，然而，间质对前列腺癌反应的分子标志物尚未完全阐明。本研究的目的是确定用硫氧还蛋白靶向纳米装置检测的基质生物标志物是否可用于区分与良性前列腺增生相关的基质和与PCA相关的基质。在这方面，我们最近证明了硫氧还蛋白靶向的纳米器件选择性地结合到冷冻的前列腺肿瘤组织切片中的反应性基质。为了实现这一点，将35名接受切除术的患者的随机冷冻前列腺组织切片与纳米装置一起孵育，并对荧光强度进行分级。每个病例的相邻切片用苏木精和伊红染色以确认诊断。选择的病例用Masson三色染色或使用硫氧还蛋白还原酶1、硫氧还蛋白还原酶2或过氧化物氧还蛋白1的抗体进行化学染色。我们的研究结果表明，使用t检验，与PCA相关的纳米器件与基质结合的分级强度显著高于（p = 0.0127）良性前列腺增生。 在代表性病例中，相邻切片的免疫组织化学染色显示，两种通常研究的硫氧还蛋白相互作用蛋白伴侣中没有一种反映了用纳米装置观察到的荧光模式。然而，硫氧还蛋白还原酶2蛋白被清楚地证明是前列腺癌相关反应性基质的生物标志物，其存在将与良性前列腺增生相关的基质与与前列腺癌相关的基质区分开。我们得出结论，与本研究中使用的抗体检测到的单个靶点相比，纳米装置检测到的信号来源于多种硫氧还蛋白相互作用蛋白伴侣，其将前列腺癌相关基质中的M2中性粒细胞和巨噬细胞相关炎症反应与良性前列腺增生中的CD4+ T淋巴细胞相关炎症区分开来。
Histological staining of reactive stroma has been shown to be a predictor of biochemical recurrence in prostate cancer, however, molecular markers of the stromal response to prostate cancer have not yet been fully delineated. The objective of this study was to determine whether or not the stromal biomarkers detected with a thioredoxin-targeted nanodevice could be used to distinguish the stroma associated with benign prostatic hyperplasia from that associated with PCA. In this regard, we recently demonstrated that a thioredoxin-targeted nanodevice selectively binds to reactive stroma in frozen prostate tumor tissue sections. To accomplish this, random frozen prostate tissue sections from each of 35 patients who underwent resection were incubated with the nanodevice and graded for fluorescent intensity. An adjacent section from each case was stained with Hematoxylin & Eosin to confirm the diagnosis. Select cases were stained with Masson's Trichrome or immunohistochemically using antibodies to thioredoxin reductase 1, thioredoxin reductase 2 or peroxiredoxin 1. Our results demonstrate that the graded intensity of nanodevice binding to the stroma associated with PCA was significantly higher (p = 0.0127) than that of benign prostatic hyperplasia using the t-test. Immunohistochemical staining of adjacent sections in representative cases showed that none of the two commonly studied thioredoxin interacting protein partners mirrored the fluorescence pattern seen with the nanodevice. However, thioredoxin reductase 2 protein was clearly shown to be a biomarker of prostate cancer-associated reactive stroma whose presence distinguishes the stroma associated with benign prostatic hyperplasia from that associated with prostate cancer. We conclude that the signal detected by the nanodevice, in contrast to individual targets detected with antibodies used in this study, originates from multiple thioredoxin interacting protein partners that distinguish the M2 neutrophil and macrophage associated inflammatory response in prostate cancer-associated stroma from the CD4+ T-Lymphocyte linked inflammation in benign prostatic hyperplasia.
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