A breakthrough may be in sight for the diagnosis and treatment of prostate cancer, the second-leading cause of cancer-related mortality in American men. Researchers have found that bringing down the levels of cholesteryl ester significantly impairs prostate cancer cell proliferation.
Cholesteryl ester storage disease is characterized by the accumulation of harmful amounts of lipids in cells and tissues throughout the body. The research involved analysis of clinical samples harvested from prostate cancer patients, specialized cell lines and mice. The study identified a link between prostate cancer aggressiveness and the compound cholesteryl ether and showed that reduction of cholesteryl ester considerably reduced the growth of prostate cancer cells, impaired its ability to invade a laboratory tissue culture, and restricted tumor growth in mice.
The findings of the study, jointly conducted by researchers associated with Purdue’s Center for Cancer Research and the Indiana University Melvin and Bren Simon Cancer Center at Indiana University School of Medicine, was published on March 4 in the journal Cell Metabolism.
The Purdue researchers did compositional analysis of individual lipid droplets in living cells and mice using an analytical tool called Raman spectromicroscopy, which they developed. Imaging data revealed an unexpected, abnormal accumulation of esterified cholesterol in lipid droplets of high-grade prostate cancer and metastases. The researchers found that cholesteryl ester accumulation is the result of metabolic activity promoting tumor growth and the loss of PTEN, a tumor-suppressing gene.
The researchers say that their findings have important implications:
- Provide a biological foundation to support the beneficial effect of cholesterol-lowering drugs
- Indicates that cholesteryl ester accumulation can be used to accurately predict prostate cancer cell proliferation
- Indicates the potential of treating cholesteryl ester to prevent the aggressive growth of prostrate cancer
Further examination of a large number of tissue biopsies and correlation assessment of cholesteryl ester levels and clinical tests would be needed to ascertain that cholesteryl ester accumulation can be used for the more accurate prediction of prostate cancer aggressiveness, say the researchers.