03 Jun Maintaining Low Cholesterol May Help Prevent Spread of Prostate Cancer
MedicalResearch.com Interview with:
Michelle Hill, PhD
Head, Precision & Systems Biomedicine Group
QIMR Berghofer Medical Research Institute
MedicalResearch.com: What is the background for this study?
Response: The role of cholesterol and cholesterol lowering drug therapy in prostate cancer has been previously investigated with mixed results. Our previous laboratory studies indicate that high cholesterol diet accelerates the spreading of advanced prostate cancer. We also observed a change of the cellular location of cholesterol, from the cell periphery (plasma membrane) to inside the cell.
This study investigates the how the change in cholesterol location promotes prostate cancer spread.
MedicalResearch.com: What are the main findings?
Response: The altered cholesterol localization led to a change in the molecules that are released in small vesicle packages (exosomes) from prostate cancer cells, which now contain the protein hnRNPK. hnRNPK normally reside in the cell nucleus, but in cells with altered cholesterol, it becomes incorporated into exosomes and released along with a range of microRNAs that help prostate cancer to spread.
Excitingly, when we reduced the cholesterol level of prostate cancer cells, or provided them omega-3 fatty acids, we were able to send hnRNPK back to the nucleus and stop the release of the pro-metastatic microRNAs.
MedicalResearch.com: What should readers take away from your report?
Response: Prostate cancer is a treatable cancer if detected early. Although further clinical trials are needed, maintaining low cholesterol may be beneficial to prevent prostate cancer spreading.
MedicalResearch.com: What further research is planned?
Response: Our pilot data in a small group of patients suggest that exosome hnRNPK may be a good indicator of metastatic cancer. We are planning to confirm this by measuring blood exosome hnRNPK in prostate cancer patient samples. If proven, then this blood test will be used to identify metastatic prostate cancer patients for cholesterol lowering therapy in a clinical trial. By selecting the patients, we may find the answer as to why the earlier studies (with all prostate cancer patients) produced mixed results.
I would like to thank my PhD student Harley Robinson for her amazing work on this project, all our collaborators and supporters.
Robinson, H, Ruelcke, JE, Lewis, A, et al. Caveolin-1-driven membrane remodelling regulates hnRNPK-mediated exosomal microRNA sorting in cancer. Clin Transl Med. 2021; 11:e381. https://doi.org/10.1002/ctm2.381
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