Phospholipids as Indicators of Castration Resistant Prostate Cancer

The association of circulating lipids with clinical outcomes of metastatic castration‐resistant prostate cancer (CRPC) is not fully understood. Interestingly, recent studies demonstrated a correlation between plasma lipids and CRPC prognosis, resulting in a proposed prognostic four‐lipid signature of (ceramide, sphingomyelin, phosphatidylcholine (PC) and phosphatidylserine (PS)). While the increase in these lipids correlated to decreased survival, the mechanisms mediating alterations in these lipids, and the correlation to resistance to treatment are not known. We addressed this gap‐in‐knowledge using in vitro models of non‐cancerous, hormone sensitive and CRPC cell lines and quantitative lipidomic analysis. An initial untargeted approach assessing both cells and media indicated that ceramides, sterols and glycerophospholipids had higher relative abundance in CRPC cells (PC‐3 and DU145), as well as hormone sensitive cells (LNCaP), as compared to a non‐cancer cell model (PNT2). Similar data was seen in media. A targeted approach focusing on lipid species shown to correlate to survival in recent publications showed significantly higher levels of 36:2 phosphatidylserine (PS) in all prostate cancer cell lines tested, and lower levels of 36:2 PC in the media of these same cells. Thus, both untargeted and targeted analysis of prostate cancer cells showed significant differences in lipidomic profiles as compared to non‐cancer prostate cells. These data suggest that the lipidomic profiles of prostate cancer cells lines mirror lipidomic profiles in the plasma of prostate cancer patients. As such, these cells may prove useful for understanding the molecular mechanism mediating lipid changes in prostate cancer patients and yield insight into the role of lipids in mediating CRPC. Support or Funding Information National Institute of Biomedical Imaging and Bioengineering NIBIB (EB0160100) Department of Defense Prostate Cancer Research Program Idea Development Award (PC150431 GRANT11996600) This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .