Epithelial Plasticity in Castration-Resistant Prostate Cancer: Biology of the Lethal Phenotype
DUKE UNIV DURHAM NC
Pagination or Media Count:
The purpose of this DOD PRTA is to investigate the role of epithelial plasticity in the promotion of metastasis in advanced prostate cancer through a sequential interrogation of biomarkers in primary prostate tumors, metastases, and circulating tumor cells CTCs. In this 2013- 2014 annual report, I provide updates on our investigation of EMT biology in both localized and metastatic prostate cancer, with particular emphasis on CTC biology as a biomarker of disease progression and metastasis. I describe our ongoing investigation into novel CTC phenotypes in men with metastatic castration-resistant prostate cancer CRPC using OB- and N-cadherin and c-met capture of CTCs, investigation of plasticity biomarkers in localized PC, and the investigation of CTCs for DNA and RNA biomarkers copy number variations and RNA Sequencing that may each shed light on the molecular pathophysiology of metastatic spread. We provide evidence for the common co-expression of epithelial and mesenchymalEMT biomarkers in CTCs from patients with metastatic castration-resistant prostate cancer CRPC as well as the common expression of stem cell biomarkers in these CTCs. This data provides strong evidence for the importance of EMT to PC metastasis in humans, but the utility of assessing mesenchymal biomarkers in localized disease is limited based on our data, particularly using a tissue microarray based assessment. These data suggest that the majority of localized prostate cancers are epithelial in phenotype but that during hematogenous dissemination, a dual epithelial-mesenchymal phenotype emerges.
- Anatomy and Physiology
- Medicine and Medical Research