SR-B1 uptake of HDL promotes prostate cancer proliferation and tumor progression

Abstract

High density lipoprotein (HDL) metabolism, in part, is facilitated by scavenger receptor class B, type 1 (SR-B1) that mediates its uptake into cells. SR-B1 is upregulated in prostate cancer tissue. Here, we report that knockout (KO) of SR-B1 via CRISPR/Cas9 editing led to reduced HDL uptake into prostate cancer cells, and reduced their proliferation in response to HDL. In vivo studies using syngeneic SR-B1 wildtype (SR-B1 +/+ ) and SR-B1 KO (SR-B1 -/-) prostate cancer cells in WT and apolipoprotein-AI KO (apoA1-KO) C57BL/6J mice showed 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 same host model. Tumor volume data was overall similar to survival data. We conclude that tumoral SR-B1 KO reduced HDL-mediated increases in prostate cancer cell proliferation and disease progression. ________________________________________