1. Uptake of high-density lipoprotein by scavenger receptor class B type 1 is associated with prostate cancer proliferation and tumor progression in mice
- Author
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Jonathan D. Smith, Kailash Gulshan, Nima Sharifi, J. Mark Brown, Emmanuel Opoku, Jennifer Major, Hanxu Lu, Shuhui Wang Lorkowski, C. Alicia Traughber, Gregory Brubaker, Aimalie Hardaway, Yoon-Mi Chung, and Chase K.A. Neumann
- Subjects
Male ,0301 basic medicine ,Biochemistry ,03 medical and health sciences ,chemistry.chemical_compound ,Prostate cancer ,High-density lipoprotein ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Scavenger receptor ,Receptor ,Molecular Biology ,Cell Proliferation ,030102 biochemistry & molecular biology ,Cell growth ,Prostatic Neoplasms ,Cell Biology ,Scavenger Receptors, Class B ,medicine.disease ,Lipids ,SCARB1 ,Up-Regulation ,Gene Expression Regulation, Neoplastic ,Mice, Inbred C57BL ,Cholesterol ,030104 developmental biology ,chemistry ,Tumor progression ,Disease Progression ,Cancer research ,lipids (amino acids, peptides, and proteins) ,Lipoproteins, HDL ,Lipoprotein - 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.
- Published
- 2020