ABSTRACT

Raftopulos NL, Washaya TC, Niederprüm A, Egert A, Hakeem-Sanni MF, Varney B, Aishah A, Georgieva ML, Olsson E, Dos Santos DZ, Nassar ZD, Cochran BJ, Nagarajan SR, Kakani MS, Hastings JF, Croucher DR, Rye KA, Butler LM, Grewal T, Hoy AJ. Prostate cancer cell proliferation is influenced by LDL-cholesterol availability and cholesteryl ester turnover. Cancer Metab. 2022 Jan 15;10(1):1. doi: 10.1186/s40170-021-00278-1.PMID: 35033184
Contact: Lisa Butler

From Movember’s Lipids and Prostate Cancer Program

ABSTRACT

This study hypothesized that castrate-resistant/advanced prostate cancer cell growth is influenced by the availability of extracellular, low-density lipoprotein (LDL)-derived, cholesterol, which is coupled to intracellular cholesteryl ester homeostasis.

C4-2B and PC3 prostate cancer cells were cultured in media supplemented with fetal calf serum (FCS), charcoal-stripped FCS (CS-FCS), lipoprotein-deficient FCS (LPDS), or charcoal-stripped LPDS (CS-LPDS) and analyzed by a variety of biochemical techniques. Cell viability and proliferation were measured by MTT assay and Incucyte, respectively.

Overall, these studies demonstrate that androgen-independent prostate cancer cell growth can be influenced by extracellular lipid levels and LDL-cholesterol availability and that uptake of extracellular cholesterol, through endocytosis of LDL-derived cholesterol and subsequent delivery and storage in the lipid droplet as cholesteryl esters, is required to support prostate cancer cell growth.

This provides new insights into the relationship between extracellular cholesterol, intracellular cholesterol metabolism, and prostate cancer cell growth and the potential mechanisms linking hypercholesterolemia and more aggressive prostate cancer.