Molecular mapping of tumor heterogeneity on clinical tissue specimens with multiplexed quantum dots.
Molecular mapping of tumor heterogeneity on clinical tissue specimens with multiplexed quantum dots.
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DOI：
10.1021/nn100213v
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发表时间：
2010-05-25
期刊：
影响因子：
17.1
通讯作者：
Nie S
中科院分区：
文献类型：
--
作者：
Liu J;Lau SK;Varma VA;Moffitt RA;Caldwell M;Liu T;Young AN;Petros JA;Osunkoya AO;Krogstad T;Leyland-Jones B;Wang MD;Nie S
肿瘤异质性是研究肿瘤发生发展机制和发展肿瘤治疗方法的重要课题之一。在这里，我们报告使用多路复用量子点（QD）和波长分辨光谱成像的分子映射的肿瘤异质性对人类前列腺癌组织标本。通过使用一组只有四种蛋白质生物标志物（E-钙粘蛋白，高分子量细胞角蛋白，p63和α-甲酰基CoA消旋酶），我们表明，结构不同的前列腺和单个癌细胞可以检测和特征的复杂微环境中的根治性前列腺切除术和针吸活检组织标本。结果揭示了广泛的肿瘤异质性在分子，细胞和建筑水平，允许直接可视化的人类前列腺腺体经历结构的转变，从双层的基底和腔细胞的恶性细胞的单层。对于临床诊断应用，多路复用QD映射提供了从传统组织染色和分子谱分析方法不可用的相关分子和形态学信息。
Tumor heterogeneity is one of the most important and challenging problems not only in studying the mechanisms of cancer development but also in developing therapeutics to eradicate cancer cells. Here we report the use of multiplexed quantum dots (QDs) and wavelength-resolved spectral imaging for molecular mapping of tumor heterogeneity on human prostate cancer tissue specimens. By using a panel of just four protein biomarkers (E-cadherin, high-molecular-weight cytokeratin, p63, and α-methylacyl CoA racemase), we show that structurally distinct prostate glands and single cancer cells can be detected and characterized within the complex microenvironments of radical prostatectomy and needle biopsy tissue specimens. The results reveal extensive tumor heterogeneity at the molecular, cellular, and architectural levels, allowing direct visualization of human prostate glands undergoing structural transitions from a double layer of basal and luminal cells to a single layer of malignant cells. For clinical diagnostic applications, multiplexed QD mapping provides correlated molecular and morphological information that is not available from traditional tissue staining and molecular profiling methods.
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