The biochemical modification of the erythrocyte membranes from women with ovarian cancer

Abstract

Summary The aim of our work was quantitative evaluation of the protein and phospholipid fractions of mature erythrocyte membranes separated from women with ovarian cancer. Blood was sampled from 30 women with ovarian cancer, aged 24-79 years, in the third stage of clinical progression of the disease. Phospholipids were separated from membranes by MOller's acidic extraction method and analysed in thinlayer two-dimensional chromatography. On the silica gel plates nine fractions of phospholipids were separated: sphingomyelin (SPH), phosphatidylethanolamine (PE), phosphatidlyserine (PS), phosphatidylcholine (PC), lysophosphatidylcholine (LPC), phosphatidic acid (PA), phosphatidylinositol (Ptd Ins), phosphatidylinositol-4-phosphate (Ptd Ins-4-P), phosphatidylinositol-4,5-diphosphate (Ptd Ins-4,5-P2). The activity of phospholipase C in erythrocyte membranes was determined by Akhrem's spectrophotometric method. Membrane proteins were separated by polyacrylamide gel electrophoresis, SDS-PAGE. It was shown that PS, SPH, LPC and PA fractions were significantly diminished. The concentration of Ptd Ins-4-P and Ptd Ins-4,5-P2 was significantly increased with simultaneous reduction in Ptd Ins level. The inhibition of phospholipase C reached 80%. The quantitative protein evaluation showed a statistically significant decrease in spectrin and a significant increase in 4.1 protein. The quantitative changes, observed in phospholipid and protein fractions, led to the restructuring of the erythrocyte membrane cytoskeleton, which may be connected to increased susceptibility to haemolysis of red blood cells.Keywords: ovarian cancer; red blood cell; phospholipid metabolism; phospholipase C; red blood cell membrane proteins Ovarian cancer is a common pathology among women over 50 years of age. Up to 2% of the female population will develop ovarian cancer during their lifetime. Cancer exerts a multidirectional influence on the human organism, leading to systemic disturbances. Mature red blood cells are a good experimental model and an easily obtainable material to study these changes. Although erythrocyte does not contain subcellular organelles it is a highly autonomic and specialized cell. That is why many biochemical transformations, difficult to evaluate in other experimental cell studies, are easily observed in erythrocytes. However, little attention has been directed to the effects of cancer on the structure of erythrocyte membrane. Lipids and proteins (Byers et al, 1985;Derick et al, 1992) are the fundamental elements of erythrocyte membrane skeleton. Phospholipids as a basic component of erythrocyte membrane determine its shape and structure and also the influence of external factors on intracellular metabolism (Ferrel et al, 1984;Schwartz et al, 1985;Smith, 1987). Erythrocyte membrane phospholipids are asymmetrically distributed in the two halves of the membrane bilayer. The choline-containing phospholipids phosphatidylcholine and sphingomyelin (PC and SPH) are present mainly in the outer monolayer, whereas the aminophospholipids...

Lack of significant differences in the corrected activity of lysophospholipase D, producer of phospholipid mediator lysophosphatidic acid, in incubated serum from women with and without ovarian tumors

“…Rather, the current results suggest that the secretion of polyunsaturated LPC by the liver into circulation declined in patients with ovarian carcinoma, since cancer exerts multidirectional influences on human organs. In advanced stages of carcinoma, the phospholipid composition of erythrocyte membranes was shown to be altered, resulting in changes in their shapes that may be associated with anemia observed in women with ovarian carcinoma, and a significant decrease in the LPC content of the erythrocyte membrane of women with ovarian carcinoma was reported 36. A reduced level of LPC in the erythrocyte membrane would be reflected by decrease in the concentration of plasma LPC.…”

Serum protein signature may improve detection of ductal carcinoma in situ of the breast

“…In addition, Alexander et al (2004) found the level of hemoglobin b-chain isoforms to be associated with breast cancer in nipple aspirate fluid, which is normally free of blood contamination. As biochemical modifications of the membrane of erythrocytes in women with ovarian cancer may increase susceptibility to hemolysis of red blood cells, a-and b-hemoglobin have been considered as potential markers for ovarian cancer (Kopczynski et al, 1998).…”

Paraneoplastic Autoimmune Hemolytic Anemia in Ovarian Cancer: A Marker of Disease Activity

“…Studies have suggested that changes in the protein and phospholipid fractions of the RBC membranes in patients with ovarian cancer lead to increases susceptibility to hemolysis. 19 It was postulated that CA-125, a glycoprotein measured in ovarian cancer, might have an immunosuppressive effect and inhibit hemolysis, which may explain AIHA after cancer treatment. 20 Specially, a study demonstrated that hemolytic serum factor from tumor was found after irradiation.…”