Background. The authors have previously demonstrated in different experimental models that sustained processes of cellular growth are characterized by alterations of cholesterol metabolism not only in the proliferating tissues but also in the plasma compartment. Methods. To evaluate whether alterations of cholesterol metabolism similar to those observed in experimental models are also associated with human cancer, in the present study cholesterol distribution in tumor tissues and lipid composition in the plasma compartment were determined in patients with different types of gastrointestinal cancer. Results. The results showed that tumor tissues contain increased amounts of cholesterol when compared with the corresponding normal tissues. Intracellular alterations of cholesterol were accompanied by specific changes of cholesterol in the plasma compartment: high‐density lipoprotein (HDL) cholesterol was markedly reduced in the serum of patients with gastrointestinal cancer and the lipoprotein profiles showed a decrease in HDL3 fraction, the main HDL subfraction in human serum. The decrease of HDL cholesterol was negatively associated with the clinical stage of the disease. No changes in either total or low‐density lipoprotein cholesterol levels were observed. Conclusions. A major function attributed to HDL is to maintain normal cell cholesterol homeostasis by removing excess of cholesterol from intracellular pools. Because the use and storage of cholesterol are increased within the tumor tissues during growth, it is possible to hypothesize that low HDL levels observed in patients with gastrointestinal cancer are associated with the increased cholesterol metabolism in proliferating tissues.

Decreased levels of HDL-C were observed in plasma of leukaemic patients, levels of total cholesterol, LDL-C, triglycerides and phospholipids were unchanged or only slightly increased. As compared to normal lymphocytes, freshly isolated leukaemic cells showed increased levels of cholesterol esters and reduction in free cholesterol. Growth stimulation of ALL and CLL cells with phytohemagglutinin led to further increase in levels of cholesterol esters. Conversely, treatment with an inhibitor of cell proliferation such as the mTOR inhibitor, RAD, caused decline in population growth rate of leukaemia cells, which was preceded by sharp reduction in rate of cholesterol esterification. On the other hand, exposure of leukaemic cells to two inhibitors of cholesterol esterification, progesterone and SaH 58-035, caused 60% reduction in their proliferation rate. In addition to demonstrating tight correlation between cell number expansion and cholesterol esterification in leukaemic cells, these results suggest that pathways that control cholesterol esterification might represent a promising targets for novel anticancer strategies.

Cholesterol distribution in tumoral tissues and lipid composition in the plasma compartment were determined in patients affected by different histologic types of lung cancer. The results showed that tumoral lung tissues contained 2-fold more total cholesterol and 3.5-fold more esterified cholesterol than normal lung tissues. In the patients the alterations in intracellular cholesterol were also associated with peculiar changes in cholesterol distribution in the plasma compartment. Serum high-density lipoprotein (HDL) cholesterol levels were markedly lower in than in controls. No significant changes in other lipid parameters were observed in these patients. We suggest that the reduced levels of serum HDL cholesterol observed in patients with lung tumors may be a consequence of the disease, probably mediated by the greater utilization of cholesterol for new membrane biogenesis and by the accumulation of esterified cholesterol in tumoral tissues.

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