Uptake of HDL-cholesterol contributes to lipid accumulation in clear cell renal cell carcinoma

Abstract

Clear cell renal cell carcinoma (ccRCC), which accounts for the majority of kidney cancer, is known to accumulate excess cholesterol. However, the mechanism and functional significance of the lipid accumulation for development of the cancer remains obscure. In this study, we analyzed 42 primary ccRCC samples, and determined that cholesterol levels of ~ 70% of the tumors were at least two-fold higher than that of benign kidney tissues. Compared to tumors without cholesterol accumulation, those containing excess cholesterol expressed higher levels of scavenger receptor BI (SR-B1), a receptor for uptake of HDL-associated cholesterol, but not genes involved in cholesterol synthesis and uptake of LDL-associated cholesterol. To further determine the roles of sterol accumulation for cancer development, we implanted ccRCC from patients into mouse kidneys using a mouse ccRCC xenograft model. Feeding mice with probucol, a compound lowing HDL-cholesterol, markedly reduced levels of cholesterol in tumors containing excess cholesterol. This treatment, however, did not affect growth of these tumors. Our study suggests that cholesterol overaccumulation in ccRCC is the consequence of increased uptake of HDL-cholesterol as a result of SR-B1 overexpression, but the lipid accumulation by itself may not play a significant role in progression of the cancer.