Mattila Simo, Tuominen Hannu, Koivukangas John, Stenbäck Frej
Department of Neurosurgery, Oulu University Hospital, Oulu, Finland.
Neuropathology. 2009 Apr;29(2):156-65. doi: 10.1111/j.1440-1789.2008.00963.x.
Prostaglandin E2 has been connected to processes promoting tumor growth in several human malignancies including gliomas. The terminal prostaglandin synthases mPGES-1, mPGES-2, and cPGES convert PGH2 into prostaglandin E2. The inhibition of their function could significantly reduce PGE2 levels in tumors while avoiding some side effects related to the inhibition of the upstream enzymes COX-1 and COX-2. In this study, the immunohistochemical staining of mPGES-1 and, for the first time, the staining of mPGES-2 and cPGES are characterized and compared with COX-1 and COX-2 staining in the same tumor samples of 94 human gliomas. The main results demonstrate over-expression of all three proteins, including cPGES and mPGES-2 that are commonly considered noninducible, in both low- and high-grade tumors. For all three proteins, average expression in tumor cells was higher in grade III tumors than grade II tumors. The analysis showed no correlation between tumor grade and staining of tumor cells or vascular endothelium with any of the antibodies except in oligodendrogliomas where moderate correlation (linear correlation coefficient 0.6; P < 0.01) could be found between tumor grade and tumor cell staining with mPGES-1 and cPGES. In grade II tumors which recurred and were reoperated upon during the data gathering period, average expression of COX-2, mPGES-1, and cPGES was higher than in tumors that were operated on only once. Our results demonstrate the significance of all three terminal prostaglandin synthases, mPGES-1, mPGES-2, and cPGES, as a possible future target of inhibition in glioma therapy.
前列腺素E2与包括神经胶质瘤在内的多种人类恶性肿瘤中促进肿瘤生长的过程有关。末端前列腺素合成酶mPGES-1、mPGES-2和cPGES将PGH2转化为前列腺素E2。抑制它们的功能可显著降低肿瘤中的PGE2水平，同时避免与抑制上游酶COX-1和COX-2相关的一些副作用。在本研究中，对mPGES-1进行了免疫组织化学染色，首次对mPGES-2和cPGES进行了染色，并与94例人类神经胶质瘤相同肿瘤样本中的COX-1和COX-2染色进行了比较。主要结果表明，在低级别和高级别肿瘤中，所有三种蛋白质均过度表达，包括通常被认为不可诱导的cPGES和mPGES-2。对于所有三种蛋白质，III级肿瘤中肿瘤细胞的平均表达高于II级肿瘤。分析表明，除少突胶质细胞瘤外，肿瘤级别与肿瘤细胞或血管内皮细胞与任何一种抗体的染色之间均无相关性，在少突胶质细胞瘤中，肿瘤级别与mPGES-1和cPGES的肿瘤细胞染色之间存在中度相关性（线性相关系数0.6；P<0.01）。在数据收集期间复发并再次手术的II级肿瘤中，COX-2、mPGES-1和cPGES的平均表达高于仅接受一次手术的肿瘤。我们的结果表明，所有三种末端前列腺素合成酶mPGES-1、mPGES-2和cPGES作为神经胶质瘤治疗中未来可能的抑制靶点具有重要意义。
