Multiplexed quantum dot labeling of activated c-Met signaling in castration-resistant human prostate cancer.

Multiplexed quantum dot labeling of activated c-Met signaling in castration-resistant human prostate cancer.
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DOI:
10.1371/journal.pone.0028670
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发表时间:
2011
期刊:
影响因子:
3.7
通讯作者:
Zhau HE
Zhau HE
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Hu P;Chu GC;Zhu G;Yang H;Luthringer D;Prins G;Habib F;Wang Y;Wang R;Chung LW;Zhau HE

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多重量子点标记(MQDL)在癌症检测和预后以及监测治疗反应方面的潜在应用引起了生物工程师、病理学家和癌症生物学家的兴趣。许多已发表的研究声称 MQDL 对于癌症生物标志物检测有效,并可用于癌症诊断和预后,但这些研究尚未针对定量生化和分子测定进行标准化。在本研究中,我们使用分子表征的人类前列腺癌细胞模型,该模型表现出激活的c-Met信号传导,上皮间质转化(EMT)以及骨和软组织的致死性转移进展作为金标准,并比较了该模型、临床人类前列腺癌组织标本和去势抵抗性人类前列腺癌异种移植模型中的c-Met细胞信号网络。我们观察到 c-Met 信号网络激活,表现为所有三个中磷酸化 c-Met 的增加。在临床前列腺癌标本和异种移植模型的单细胞水平上,下游生存信号网络由 NF-κB 和 Mcl-1 介导,EMT 由 NF-κB 配体受体激活剂 (RANKL) 驱动。结果通过实时 RT-PCR 和蛋白质印迹在人类前列腺癌细胞模型中得到证实。 MQDL 是评估生物标志物表达的强大工具,它以高度的灵敏度提供细胞和组织水平上癌症进展的分子洞察。
The potential application of multiplexed quantum dot labeling (MQDL) for cancer detection and prognosis and monitoring therapeutic responses has attracted the interests of bioengineers, pathologists and cancer biologists. Many published studies claim that MQDL is effective for cancer biomarker detection and useful in cancer diagnosis and prognosis, these studies have not been standardized against quantitative biochemical and molecular determinations. In the present study, we used a molecularly characterized human prostate cancer cell model exhibiting activated c-Met signaling with epithelial to mesenchymal transition (EMT) and lethal metastatic progression to bone and soft tissues as the gold standard, and compared the c-Met cell signaling network in this model, in clinical human prostate cancer tissue specimens and in a castration-resistant human prostate cancer xenograft model. We observed c-Met signaling network activation, manifested by increased phosphorylated c-Met in all three. The downstream survival signaling network was mediated by NF-κB and Mcl-1 and EMT was driven by receptor activator of NF-κB ligand (RANKL), at the single cell level in clinical prostate cancer specimens and the xenograft model. Results were confirmed by real-time RT-PCR and western blots in a human prostate cancer cell model. MQDL is a powerful tool for assessing biomarker expression and it offers molecular insights into cancer progression at both the cell and tissue level with high degree of sensitivity.
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