The human breast carcinoma cell line HBL-100 acquires exogenous cholesterol from high-density lipoprotein via CLA-1 (CD-36 and LIMPII analogous 1)-mediated selective cholesteryl ester uptake

Abstract

Aberrant cell proliferation is one of the hallmarks of carcinogenesis, and cholesterol is thought to play an important role during cell proliferation and cancer progression. In the present study we examined the pathways that could contribute to enhanced proliferation rates of HBL-100 cells in the presence of apolipoprotein E-depleted high-density lipoprotein subclass 3 (HDL(3)). When HBL-100 cells were cultivated in the presence of HDL(3) (up to 200 microg/ml HDL(3) protein), the growth rates and cellular cholesterol content were directly related to the concentrations of HDL(3) in the culture medium. In principle, two pathways can contribute to cholesterol/cholesteryl ester (CE) uptake from HDL(3), (i) holoparticle- and (ii) scavenger-receptor BI (SR-BI)-mediated selective uptake of HDL(3)-associated CEs. Northern- and Western-blot analyses revealed the expression of CLA-1 (CD-36 and LIMPII analogous 1), the human homologue of the rodent HDL receptor SR-BI. In line with CLA-1 expression, selective uptake of HDL(3)-CEs exceeded HDL(3)-holoparticle uptake between 12- and 58-fold. Competition experiments demonstrated that CLA-1 ligands (oxidized HDL, oxidized and acetylated low-density lipoprotein and phosphatidylserine) inhibited selective HDL(3)-CE uptake. In line with the ligand-binding specificity of CLA-1, phosphatidylcholine did not compete for selective HDL(3)-CE uptake. Selective uptake was regulated by the availability of exogenous cholesterol and PMA, but not by adrenocorticotropic hormone. HPLC analysis revealed that a substantial part of HDL(3)-CE, which was taken up selectively, was subjected to intracellular hydrolysis. A potential candidate facilitating extralysosomal hydrolysis of HDL(3)-CE is hormone-sensitive lipase, an enzyme which was identified in HBL-100 cells by Western blots. Our findings demonstrate that HBL-100 cells are able to acquire HDL-CEs via selective uptake. Subsequent partial hydrolysis by hormone-sensitive lipase could provide 'free' cholesterol that is available for the synthesis of cellular membranes during proliferation of cancer cells.

Expression of the Scavenger Receptor Class B type I (SR-BI) family in Drosophila melanogaster

“…It binds to apoptotic thymocytes and acts as a lipoprotein receptor (Calvo and Vega, 1993;Murao et al, 1997;Pussinen et al, 2000); LIMPII localizes in lysosomal membranes and it is implicated in cell adhesion (Vega et al, 1991); SR-BI is located in fat, lung, liver, ovary and adrenal gland, being also a lipoprotein receptor (Acton et al, 1994;Rigotti et al, 1995). Multiple orthologues of this family have been identified in invertebrates.…”

Expression analysis of apolipoprotein E and its associated genes in gastric cancer

“…Accumulating evidence indicates that in vivo tumors and tumor cell lines undergo abnormal changes in cholesterol metabolism (6,7). In theory, rapidly dividing cancer cells utilize two major mechanisms, in order to fulfill their cholesterol requirements (8).…”

Role of HDL in cholesteryl ester metabolism of lipopolysaccharide-activated P388D1 macrophages

“…It is well known that CEs, in specialized tissues such as the adrenal cortex and liver ( 56 ), are taken up directly from HDLs ( 57 ) by a plasma-membrane scavenger receptor protein (SR-B1) in rodents ( 49 ), and CLA-1 in humans ( 58 ). Furthermore, a selective uptake of CE-HDLs by SR-B1 has been described in rapidly proliferating tumor cells ( 50,58,59 ).…”