Changes in electric charge and phospholipids composition in human colorectal cancer cells.
ABSTRACT Cancer cells perform their malicious activities through own cell membranes that screen and transmit inhibitory and stimulatory signals out of the cells and into them. This work is focused on changes of phospholipids content (PI-phosphatidylinositol, PS-phosphatidylserine, PE-phosphatidylethanolamine, PC-phosphatidylcholine) and electric charge that occur in cell membranes of colorectal cancer of pT 3 stage, various grades (G2, G3) and without/with metastasis. Qualitative and quantitative composition of phospholipids in the membrane was determined by HPLC (high-performance liquid chromatography). The surface charge density of colorectal cancer cell membranes was measured using electrophoresis. The measurements were carried out at various pH of solution. It was shown that the process of cancer transformation was accompanied by an increase in total amount of phospholipids as well as an increase in total positive charge at low pH and total negative charge at high pH. A malignant neoplasm cells with metastases are characterized by a higher PC/PE ratio than malignant neoplasm cells without metastases.
- SourceAvailable from: Sophia Ran[show abstract] [hide abstract]
ABSTRACT: Anionic phospholipids are largely absent from the external leaflet of the plasma membrane of mammalian cells under normal conditions. Exposure of phosphatidylserine on the cell surface occurs during apoptosis, necrosis, cell injury, cell activation, and malignant transformation. In the present study, we determined whether anionic phospholipids become exposed on tumor vasculature. A monoclonal antibody, 9D2, which specifically recognizes anionic phospholipids, was injected into mice bearing a variety of orthotopic or ectopic tumors. Other mice received annexin V, a natural ligand that binds to anionic phospholipids. Both 9D2 and annexin V specifically localized to vascular endothelium in all of the tumors, and also to tumor cells in and around regions of necrosis. Between 15 and 40% of endothelial cells in tumor vessels were stained. No localization was detected on normal endothelium. Various factors and tumor-associated conditions known to be present in the tumor microenvironment were examined for their ability to cause exposure of anionic phospholipids in cultured endothelial cells, as judged by 9D2 and annexin V binding. Hypoxia/reoxygenation, acidity, thrombin, and inflammatory cytokines all induced exposure of anionic phospholipids. Hydrogen peroxide was also a strong inducer. Combined treatment with inflammatory cytokines and hypoxia/reoxygenation had greater than additive effects. Possibly, injury and activation of tumor endothelium by cytokines and reactive oxygen species induce exposure of anionic phospholipids, most likely phosphatidylserine. Anionic phospholipids on tumor vessels could potentially provide markers for tumor vessel targeting and imaging.Cancer Research 12/2002; 62(21):6132-40. · 8.65 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Risk of gastrointestinal cancers is closely related to increased levels of oxidants in the balance between oxidant and anti-oxidant agents. A possible explanation of this epidemiological observation is the local loss of the epithelial barrier function with a focal inflammatory response. Accordingly, chronic inflammatory diseases represent well-known risk factors for cancer and, on the other hand, it is known that anti-inflammatory agents, demulcents and antioxidants markedly inhibit the development of colon cancer in animal models as well in humans. At molecular level a key role in the process that link inflammation to cellular transformation seems to be played by activation of Cyclooxygenase-2 (COX-2) together with production of Reactive Oxygen Intermediate (ROI). Both these events have been strictly linked with cell proliferation and transformation, although the intracellular pathways involved in these processes are still not completely understood. The uncontrolled proliferation, which is a landmark of cellular transformation, is accompanied by the deregulation of proteins involved in the control of cell cycle checkpoints. Altered expression and function of cyclooxygenase and nitric oxide synthase seem to influence, among others, the expression of proteins involved in the regulation of cell cycle progression. Similarly, anti-inflammatory and antioxidant agents may also act on the expression and function of several cell cycle regulating proteins. Understanding the mechanisms by which chronic inflammation contributes to genetic and epigenetic changes involved in the regulation of critical cell cycle checkpoints may help to develop more and more specific treatment strategies for reducing malignant transformation of these inflammatory diseases.Current Pharmaceutical Design 02/2004; 10(14):1653-66. · 3.31 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Colorectal cancer has a high incidence of morbidity and mortality in the North American population. Elevated levels of plasmalogens have been reported in some neoplastic tissues including colon tumors, but the mechanism for this increase has not been defined. Since changes in plasmalogen level are usually associated with changes in the other phospholipid subclasses, a general increase in all phospholipid subclasses may also be found in colonic neoplasms. In this study, the levels of the major phospholipids, including their plasmalogen and diacylphospholipid subclasses, were found to be elevated in human malignant colonic tissues. Since phosphatidylcholine is the most prominent type of phospholipid found in both malignant and control tissues, the mechanism for its accumulation during malignancy was investigated. Decreases in phospholipase C and D activities were observed in tumor samples, but an enhancement of the CTP: phosphocholine cytidylyltransferase activity was also detected. Immunoblotting analysis revealed that the elevated cytidylyltransferase activity was caused by a three-fold increase in the level of enzyme protein during tumor development. Based on these enzyme studies, we conclude that the high level of phosphatidylcholine in colon tumors resulted from a decrease in its turnover and an increase in its expression.Molecular and Cellular Biochemistry 10/1996; 162(2):97-103. · 2.33 Impact Factor