Marked hypocholesterolemia in a case with adrenal adenoma--enhanced catabolism of low density lipoprotein (LDL) via the LDL receptors of tumor cells.

Abstract

A 16-yr-old girl was hospitalized because of amenorrhea and virilism, and was diagnosed with an adrenal tumor on the right side. Her serum androgen levels were markedly elevated, and severe hypocholesterolemia (total cholesterol, 0.59 mmol/L) was observed. After resection of the tumor, her serum cholesterol level dramatically rose to normal, suggesting a role of this tumor in her marked hypocholesterolemia. To investigate the mechanism of hypocholesterolemia in this case, we examined the effects of dehydroepiandrosterone and dehydroepiandrosterone sulfate on the low density lipoprotein (LDL) receptor activity of fibroblasts. These hormones did not have any effect on LDL receptor activity. Northern blot analysis demonstrated that the LDL receptor messenger ribonucleic acid level of this tumor tissue was increased about 8-fold compared with that of normal adrenal cortex. The LDL receptor activity of the cultured cells established from this tumor was 2-fold higher than that of Hep G2 cells. Furthermore, the LDL receptor activity could not be down-regulated by an excessive dose of 25-hydroxycholesterol. These results suggest that increased LDL receptor activity and unrestricted uptake of LDL by the adrenal tumor may have caused the marked hypocholesterolemia in this patient.

LDL, HDL and endocrine-related cancer: From pathogenic mechanisms to therapies

“…Both human LDL-and HDL-C were used for steroid production by primary adrenocortical cells obtained from adenomas [238]. These findings were also found in adrenocortical carcinoma cells, mainly by the action of LDLR and SR-BI [239,240]. In the latter report, the tumor tissue of the female patient expressed high levels of LDLR and a severe reduction in LDL-C and HDL-C. More importantly, her serum cholesterol levels were normalized few days after tumor removal [240].…”

Lipoproteins as Markers for Monitoring Cancer Progression

“…In vitro and in vivo studies demonstrate that LDL-C is increasingly associated with carcinogenesis. This has been attributed to an increase in LDL-C uptake and receptor activity [46][47][48][49][50][51][52]. Additionally, oxidative stress can induce carcinogenesis and oxidation of low-density lipoprotein.…”

Low Density Lipid Nanoparticles for Solid Tumor Targeting

“…It is reported that these LDL receptors are overexpressed on different types of solid tumors like colon cancer [ 11 ], prostate tumors [ 12 ], adrenal tumors [ 13 ], hormone unresponsive breast tumors [ 14 ], cancers of gynecological origin [ 15 ], malignant brain tumors [ 16 ], lung tumor tissues [ 17 ], and leukemia [ 18 – 21 ]. The reason might be that in a pathological condition like solid tumor growth, the rapidly dividing cells require high cholesterol content and therefore, LDL receptors are overexpressed so that plasma-derived LDL could mobilize the cholesterol for the rapidly dividing cancer cells.…”