Early Detection of Castration-Resistant Prostate Cancer by Assessing Interactions Between Circulating Tumor Cells and Accompanying Immune Cells
Abstract
Prostate cancer (PCa) is the most frequently diagnosed cancer in men. In majority of "castration sensitive" patients proliferation of cancer cells can be attenuated by the androgen deprivation therapy (ADT). Unfortunately, many patients develop "castration resistance" (CR) followed by metastatic spread. For effective second-line therapy the resistance needs to be detected early. We postulate that mechanical and immunochemical profiling of blood-isolated "seeds of metastasis" (circulating tumor cells; CTCs) points at CTCs aggressiveness indicating risk of CR. Our specific aims call for determining the role of (1) epithelial-mesenchymal transition (EMT) and (2) interactions with circulating macrophages in survival-promoting mechanical fitness of CTCs. Based on profiling of CTCs and model cultured cells we plan to (3) construct a predictive model for early CR detection. In this reporting period we met the goal for accrual of patients starting ADT and for profiling of patient-isolated CTCs. Consistent with our hypothesis, we detected unique invasiveness-indicating hybrid EMT features in patients' CTCs and model PCa cells co-cultured with model macrophages. To improve fidelity of our cell culture model of acquired aggressiveness, we introduced circulation-simulating fluid shear stress, with very promising initial results. The outcomes include a manuscript submitted and a poster presented with the abstract published.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2019
- Accession Number
- AD1088704
Entities
People
- Maria Gaczyńska
- Pawel A. Osmulski
- Tim H. Huang
Organizations
- University of Texas Health Science Center at San Antonio