Epithelial Plasticity in Castration-Resistant Prostate Cancer: Biology of the Lethal Phenotype
Annual summary 1 Jul 2010-30 Jun 2011
DUKE UNIV DURHAM NC
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The purpose of this DOD PRTA is to investigate the role of epithelial plasticity in the promotion of metastasis in advanced prostate cancer PC through the interrogation of biomarkers in primary PC, metastases, and circulating tumor cells CTCs. Epithelial plasticity biomarkers inclusive of epithelial-mesenchymal transition EMT and stemness phenotypes were evaluated in a prospective correlative study of men with metastatic castration-resistant PC in which CTCs were collected and analyzed. These results unequivocally demonstrated that the preponderance 80 of CTCs from these men co-expressed both epithelial cytokeratin, EpCAM, E-cadherin and mesenchymal N- and O-cadherin, vimentin and stemness CD133 proteins. These results are published in Molecular Cancer Research and provide the strongest direct evidence to date for the existence of EMT in human cancer. In year 1, we have also begun to analyze EMT marker expression in a tissue microarray of radical prostatectomy specimens linked to long-term follow up. Initial results suggest feasibilityvalidity, and we are in the process of antibody optimization for additional studies of EMTstemness as it relates to prostate cancer recurrence. We have also begun a collaborative research process with Veridex to develop a novel CTC capture ferrofluid to identify non-epithelial CTCs from the blood of men with CRPC.
- Anatomy and Physiology
- Medicine and Medical Research