High-density lipoprotein (HDL) cholesterol could provide a novel treatment target for patients with lymphoma, US scientists believe.
The researchers report the efficacy of synthetic gold HDL nanoparticles (NPs) in cell studies and a mouse model of B-cell lymphoma in the Proceedings of the National Academy of Sciences USA.
"We have shown that HDL-NPs are biologically functional nanostructures that may provide a new paradigm for the treatment of lymphoma," explain Leo Gordon (Northwestern University Feinberg School of Medicine, Chicago, Illinois) and co-authors.
They found that the scavenger receptor (SR)-B1, which has high affinity for HDL cholesterol, is expressed on the surface of multiple B-cell lymphoma cells lines but not on healthy human lymphocytes.
HDL NPs had a two-pronged attack on lymphoma cells: competing for SR-B1 receptors with HDL cholesterol and thereby reducing HDL cholesterol uptake, and also by increasing cholesterol efflux in lymphoma cells. But HDL NPs did not manipulate cholesterol efflux in healthy cells.
Moreover, NP treatment led to a dose-dependent increase in apoptosis in lymphoma cells lines but did not induce cell death in healthy human lymphocytes, macrophages, or hepatocytes exposed in vitro.
In mice bearing human B-cell lymphoma flank xenografts, animals given HDL NPs had significantly smaller tumor volumes than animals given HDL cholesterol or a control treatment.
The researchers explain that lymphoma and leukemia have previously been shown to have elevated uptake of HDL cholesterol, while reducing HDL cholesterol availability is known to fight Epstein Barr virus infection, related to Burkitt's lymphoma.
"Increased expression of SR-B1 by B-cell lymphoma cells may provide a mechanism to
outcompete other tissues for cholesterol, cholesteryl esters, or viral promoters of cell growth and proliferation," they hypothesize.
Commenting in a press release, Gordon said: "This has the potential to eventually become a nontoxic treatment for B-cell lymphoma which does not involve chemotherapy. It's an exciting preliminary finding."
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