Lipidomic Analysis of Media from Castration and Drug Resistant Prostate Cancer Cells
Abstract
Castration‐resistant prostate cancer (CRPC) is a severe, metastatic form of prostate cancer (PCa). Several treatment modalities have been approved during the past decade by the FDA for treating CRPC patients. Unfortunately, a high percentage of patients fail to respond to these treatments for several reasons, including developing resistance. One reason for these failures is inadequate methods that allow for accurate staging of PCa. This poses a diagnostic problem that limits our ability to create a patient‐centered treatment plan. We addressed this problem by testing the hypothesis that an association exists between circulating lipids and clinical outcomes of CRPC. This hypothesis is based on recent studies demonstrating a correlation between plasma lipids and CRPC prognosis. To understand this correlation, we used in vitro models of non‐cancerous, hormone‐sensitive, and drug‐resistant CRPC cell lines combined with quantitative lipidomic analysis to study the correlation between CRPC and lipid profiles. An untargeted approach indicated that media from hormone sensitive cells (LNCaP), and CRPC cells (DU145) had lower relative abundance of glycerophospholipids, as compared to a non‐cancer cell model (PNT2). However, drug resistant cells (DU145 DR) and their media had a higher abundance of glycerophospholipids such as phosphatidylinositol (PI), phosphatidic acid (PA), and phosphatidylserine (PS) as compared to parent control (DU145). These data confirm previous in vivo findings and suggest that the lipidomic profiles of PCa cells lines mirror lipidomic profiles in the plasma of PCa patients. Further, these data provide an in vitro model to investigate the molecular mechanisms mediating lipidomic changes during the progression of drug resistant PCa.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 01, 2019
- Source ID
- 10.1096/fasebj.2019.33.1_supplement.509.8
Entities
People
- Brian S Cummings
- Lishann M. Ingram
- Maryam Mansoura
Organizations
- National Institute of Biomedical Imaging and Bioengineering
- United States Department of Defense
- University of Georgia