Cholesterol metabolism and lipid droplet vacuoles; a potential target for the therapy of aggressive lymphoma

• Published in: Journal of Clinical and Experimental Hematopathology Vol. 62; no. 4; pp. 190 - 194
• Main Authors: Yano, Hiromu, Fujiwara, Yukio, Komohara, Yoshihiro
• Format: Journal Article
• Language: English
• Published: Japan The Japanese Society for Lymphoreticular Tissue Research 01-01-2022; JSLRT
• Subjects: ACAT1; Adult; Cholesterol - metabolism; Humans; LDLR; Lipid Droplets - metabolism; lipid metabolism; Lymphoma; Review; Scavenger Receptors, Class B - metabolism; SR-BI; Vacuoles - metabolism; SR-BI; LDLR; lipid metabolism; lymphoma; ACAT1
• ISSN: 1346-4280; 1880-9952
• DOI: 10.3960/jslrt.22023

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.