Epithelial Plasticity in Castration-Resistant Prostate Cancer: Biology of the Lethal Phenotype
Abstract
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 feasibility/validity, and we are in the process of antibody optimization for additional studies of EMT/stemness 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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2011
- Accession Number
- ADA548606
Entities
People
- Andrew J. Armstrong
Organizations
- Duke University