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Prostate Cancer Research

Progress Report: Andrew Armstrong, MD, MSc

Investigator: Andrew Armstrong, MD, MSc – Associate Professor, Duke University

Linking Epithelial and Stemness Plasticity with Prostate Cancer Metastasis and the Lethal Phenotype 

The mechanism by which cancer cells spread from the primary tumor to distant sites in the body (the process of metastasis) is not fully understood. Scientists hypothesize that prostate cancer cells change their morphology from an epithelial (cube-like shaped cells with “sticky” proteins that provide cell-to-cell adhesion) to a mesenchymal cell (elongated shaped cells with fewer “sticky” proteins and capable of cell movement) to facilitate release from the tumor and entry into circulation – an early step in the process of metastasis. This phenomenon is termed epithelial-to-mesenchymal transition (EMT). It is believed that tumor cells undergo EMT and use the blood stream as a conduit to travel to other sites in the body where they develop new sites of tumor growth.

In the past decade a technology has been developed to capture and isolate circulating tumor cells (CTCs) from the blood (Veridex/Cell Search System). However, these CTC capture methods can only recognize epithelial prostate cancer cells. Dr. Armstrong is interested in assessing whether there are mesenchymal prostate cancer cells circulating in the blood. Using the FDA-approved Veridex CTC capture system as a platform, Dr. Armstrong and colleagues have successfully developed a method to measure CTCs that are mesenchymal-like. Analysis of blood from both metastatic breast cancer and metastatic castration resistant prostate cancer patients showed that the majority of patients had mesenchymal-like CTCs, 67-82% and 81-86%, respectively, depending on the type of mesenchymal marker used. The team found that these CTCs exhibited several characteristics specific to mesenchymal and stem-like cells.  In a study using only prostate cancer specimens, Dr. Armstrong found that even though most patients had mesenchymal CTCs, cells in metastatic tumor sites were predominately characterized by epithelial markers. This provokes the hypothesis that prostate cancer cells undergo EMT to leave the primary tumor and then go through mesenchymal-to-epithelial transition (MET) to generate metastatic tumors in distant sites. These findings indicate that the current CTC capture system is under-detecting CTCs in many patients and that methods to develop improved detection techniques based on these findings could improve the usefulness of CTC tests. Dr. Armstrong plans to continue investigating the biology of metastasis in an attempt to describe the biology of tumor progression that results in lethal metastatic disease.  A comprehensive understanding of the mechanisms of metastasis may inform new therapeutic targets and personalized medicine that could prevent or delay and better treat prostate cancer metastases.

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