Abstract
Cancer cells are hungry of cholesterol incorporated from serum with avidity and used to favour the expressions of proteins involved in cell proliferation such as RNA polymerase II, STAT3, PKCz and cyclin D1. Numerous studies have shown that exists a strong interaction between unesterified cholesterol and saturated fatty acid sphingomyelin which arises from the Van der Waals interaction. Since sphingomyelin and cholesterol association is responsible for the formation of membrane lipid raft involved in cell signalling, we studied the possible hyposphingomyelinemia associated to hypocholesterolemia in the patients with cancer. The blood of 23 patients with monoclonal gammopathy were analyzed for cholesterol, 12:0 sphingomyelin, 16:0 sphingomyelin and 18:1sphingomyelin content. The results demonstrated that only the patients with very low level of cholesterol (65-99 mg/dl) had low amount of sphingomyelin and, in particular, of saturated sphingomyelin specie (16:0 sphingomyelin). The possibility that the hypocholesterolemia in cancer was secondary to hyposphingomyelinemia was discussed.
Highlights
Lipids are structural and functional molecules localized in cell membranes and in the nucleus where interact with active chromatin and play specific roles in cell proliferation, differentiation, apoptosis and cancer [1]
CHO is incorporated in cancer cells from serum with avidity and used to favour the expressions of proteins involved in cell proliferation such as RNA polymerase II, STAT3, PKCz and cyclin D1 [2]
The lipid microdomains, known as lipid rafts, are platforms for specific proteins involved in cell signaling if they are localized in cell membrane and are platforms for DNA duplication and transcription if they are associated to the inner nuclear membrane [4,5]
Summary
Lipids are structural and functional molecules localized in cell membranes and in the nucleus where interact with active chromatin and play specific roles in cell proliferation, differentiation, apoptosis and cancer [1]. In particular CHO has an important role in regulating the synthesis of invadopodia: protrusion in the cell membrane of some cells, displaying properties of SM and CHO-enriched membranes or lipid rafts frequently seen in invasive and metastatic cancer cells that invade surrounding tissues [7]. It remains unclear how the rafts are formed in cancer cells, i.e., if using lipids that incorporate from the blood, reducing their physiological values.There is evidence that low levels of serum CHO-phospholipids are associated with the antiphospholipid antibodies in monoclonal gammopathy [8]. We analysed the main species of SM by SM/SM-UFLC in order to highlight the changes of saturated fatty acid SMs that interact with CHO
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