Prostaglandin E2 levels in human brain tumor tissues and arachidonic acid levels in the plasma membrane of human brain tumors
Introduction
Polyunsaturated fatty acids, especially docosahexaenoic acid and arachidonic acid, are enriched in brain lipids [22]where they are major components of excitable membranes [2]. Arachidonic acid is stored intracellularly in membrane phospholipids and released when the cell is activated by appropriate stimuli [27]. Arachidonic acid is further metabolized in a cascade through the cyclooxygenase and lipoxygenase pathways, eventually producing such physiologically active substances as prostaglandins and leukotrienes [13]. Changes in the membrane phospholipid fatty acid composition can alter the amount of arachidonic acid contained in the cell membrane. This can affect the amount of prostaglandins [27].
Increased biosynthesis of prostaglandins, particularly of the E series, has been demonstrated in a large number of human and experimental cancers, including breast cancer [8], colon cancer 25, 31, head and neck cancer [16]and lung cancer [21]. These compounds may play an important role in tumor growth and spread [7]. The growth of many experimental tumors is suppressed by the administration of low non-toxic doses of cyclooxygenase inhibitors such as indomethacin, aspirin and piroxicam [12]. This indicates that, in many cases, tumor prostaglandin synthesis contributes positively to tumor growth. The mechanisms involved are unclear, but considerable evidence implicates prostaglandin E2 (PGE2) as an immunosuppressive molecule that acts to downregulate host antitumor reactions [9].
Little is known of the production of prostaglandins by intracranial tumors. Certain authors reported that PGE2 levels increase in brain tumors and that PGE2 is produced in the greatest amount in meningiomas [7]. By contrast, other authors reported no increased production of PGE2 in brain tumors [11]. The present study was designed to investigate the levels of arachidonic acid in the cell membrane of human brain tumors and the levels of PGE2 in brain tumor tissues.
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Materials and methods
Tumor or brain tissue was obtained from patients undergoing craniotomy at the Department of Neurosurgery, Cerrahpaşa Medical Faculty. Twenty-two tumor samples were studied, including 10 gliomas, seven meningiomas, two metastatic tumors, two schwannomas and one medulloblastoma. Histologically normal adjacent brain tissues to tumor tissues were studied as a control group. After removal, surgical specimens were immediately frozen in liquid nitrogen and stored at −70°C until they were assayed. A
Results and discussion
Arachidonic acid levels of tumor and control brain tissues are shown in Table 1. The levels of arachidonic acid in gliomas (n=9) and meningiomas (n=6) were significantly higher than those of control tissues (n=12) (P=0.000 and P=0.000, respectively). The levels of arachidonic acid in two schwannomas, one metastatic tumor and one medulloblastoma were found to be higher than those of control brain tissue, although the statistical significance could not be analyzed.
PGE2 levels of tumor and control
Acknowledgements
This work was supported by the Research Fund of The University of Istanbul. Project Number: T-15/170395.
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