Cholesterol uptake via
LDL receptor (LDLR) is increased in some malignant
tumors, and incorporated
LDL contribute to lipid droplet formation.
Burkitt's lymphoma is known to have a large number of vacuoles in the cytoplasm, however, intracellular vacuoles are also seen in
high-grade lymphomas such as
adult T-cell leukemia/lymphoma,
diffuse large B-cell lymphoma and primary central nervous system
lymphoma. Recent studies have shown that esterified
cholesterol is the main component of these vacuoles and the expression of
cholesterol metabolism-related molecules such as LDLR,
acetyl-CoA acetyltransferase 1 (ACAT1) which esterifies free
cholesterol, and
scavenger receptor class B type I (SR-BI) which effluxes free
cholesterol, was significantly upregulated in
lymphoma cells. Moreover, negative feedback of LDLR was not regulated even under
cholesterol-rich conditions in
lymphoma cells. We found that cytoplasmic free
cholesterol was increased by ACAT and SR-BI inhibitors (
CI-976 and BLT-1, respectively), and the accumulation of free
cholesterol induced
lymphoma cell apoptosis. In addition, overexpression of lipid droplet
surface proteins has been correlated with poor prognosis in several malignant
tumor such as
ovarian cancer and
clear cell renal cell carcinoma, and it is important to evaluate lipid droplet formation in malignant
tumors including
lymphomas.