Uptake of high-density lipoprotein by scavenger receptor class B type 1 is associated with prostate cancer proliferation and tumor progression in mice
Year: 2020
Type: article
Abstract: High-density lipoprotein (HDL) metabolism is facilitated in part by scavenger receptor class B, type 1 (SR-B1) that mediates HDL uptake into cells. Higher levels of HDL have been associated with protection in other diseases, however, its role in prostate cancer is not definitive. SR-B1 is up-regulated in prostate cancer tissue, suggesting a possible role of this receptor in tumor progression. Here, we report that knockout (KO) of SR-B1 in both human and mouse prostate cancer cell lines through CRISPR/Cas9-mediated genome editing reduces HDL uptake into the prostate cancer cells and reduces their proliferation in response to HDL. In vivo studies using syngeneic SR-B1 WT (SR-B1 +/+ ) and SR-B1 KO (SR-B1 −/− ) prostate cancer cells in WT and apolipoprotein-AI KO (apoA1-KO) C57BL/6J mice revealed that WT hosts, containing higher levels of total and HDL-cholesterol, grew larger tumors than apoA1-KO hosts with lower levels of total and HDL-cholesterol. Furthermore, SR-B1 −/− prostate cancer cells formed smaller tumors in WT hosts than SR-B1 +/+ cells in the same host model. Increased tumor volume was overall associated with reduced survival. We conclude that knocking out SR-B1 in prostate cancer tumors reduces HDL-associated increases in prostate cancer cell proliferation and disease progression.
Source: Journal of Biological Chemistry
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
Funders: American Heart Association, Cleveland Clinic, Case Comprehensive Cancer Center, Case Western Reserve University, National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: Molecular Medicine Training Program, G3228222705, G3865812744, Compensatory steroidogenesis mechanisms in castration-resistant prostate cancer, G4870427513, Gut Microbiota and Cardiometabolic Diseases, G5964267849, The Role of PPAR in Human Placental Development and Preeclampsia, The Role of Bacterial Choline Metabolism in Host Stress Responses, Opposing Effects of HDL Metabolism on Prostate Cancer, ApoA1 lipidation by ABCA1 in HDL biogenesis, G8180661338, G8634843517, G87592374, Alcohol and tissue injury, from mechanisms to treatments, Phosphatidylinositol Metabolism and Trafficking in Atherosclerosis and Inflammation, Case Comprehensive Cancer Center Support Grant
OpenAlex ID: W3021273165