Cancer Letters

Cancer Letters

Volume 132, Issues 1–2, 23 October 1998, Pages 17-21
Cancer Letters

Prostaglandin E2 levels in human brain tumor tissues and arachidonic acid levels in the plasma membrane of human brain tumors

https://doi.org/10.1016/S0304-3835(98)00127-XGet rights and content

Abstract

Arachidonic acid is stored in the cell membrane and released when the cell is activated by appropriate stimuli. It is the substrate for prostaglandins. Both experimental and human tumors often synthesize high levels of prostaglandins, most notably prostaglandin E2 (PGE2). Some experiments suggest that these compounds increase tumor growth through their actions on host immunocytes. In this study, 22 patients with various brain tumors and 12 control brain tissues were studied. PGE2 levels in tissue samples were measured by ELISA. Arachidonic acid levels in the plasma membrane of tissue samples were analyzed by capillary gas chromatography. The levels of PGE2 were significantly higher in gliomas (n=10) and meningiomas (n=7) compared with control tissues (P=0.000 and P=0.000, respectively). Also, PGE2 levels in meningiomas were significantly higher than in gliomas (P=0.000). Arachidonic acid levels in the plasma membrane of gliomas (n=9) and meningiomas (n=6) were significantly higher than in the control tissues (P=0.000 and P=0.000, respectively). These results suggest that the increased production of PGE2 may suppress the immune system and play an important role in tumor growth.

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.

Section snippets

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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