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Multiplexed Quantum Dot Labeling of Activated c-Met Signaling in Castration-Resistant Human Prostate Cancer

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posted on 21.08.2012, 00:00 by Peizhen Hu, Gina C.-Y. Chu, Guodong Zhu, Hua Yang, Daniel Luthringer, Gail Prins, Fouad Habib, Yuzhuo Wang, Ruoxiang Wang, Leland W. K. Chung, Haiyen E. Zhau
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-kB and Mcl-1 and EMT was driven by receptor activator of NF-kB 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.

Funding

This work is supported by research grants 2PO1CA098912 and 1RO1CA122602 of the National Institutes of Health/National Cancer Institute, and Prostate Cancer Foundation Challenge Award (LWK Chung). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Publisher Statement

© 2011 Hu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. DOI: 10.1371/journal.pone.0028670

Publisher

Public Library of Science

Language

en_US

issn

1932-6203

Issue date

21/12/2011

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