Institute for Vascular Signalling, Centre for Molecular Medicine, Goethe University, 60590 Frankfurt, Germany.
Institute of Biochemistry I, Faculty of Medicine, Goethe University, 60590 Frankfurt, Germany.
Int J Mol Sci. 2021 Jul 1;22(13):7120. doi: 10.3390/ijms22137120.
Epoxides and diols of polyunsaturated fatty acids (PUFAs) are bioactive and can influence processes such as tumor cell proliferation and angiogenesis. Studies with inhibitors of the soluble epoxide hydrolase (sEH) in animals overexpressing cytochrome P450 enzymes or following the systemic administration of specific epoxides revealed a markedly increased incidence of tumor metastases. To determine whether PUFA epoxides increased metastases in a model of spontaneous breast cancer, sEH mice were crossed onto the polyoma middle T oncogene (PyMT) background. We found that the deletion of the sEH accelerated the growth of primary tumors and increased both the tumor macrophage count and angiogenesis. There were small differences in the epoxide/diol content of tumors, particularly in epoxyoctadecamonoenic acid versus dihydroxyoctadecenoic acid, and marked changes in the expression of proteins linked with cell proliferation and metabolism. However, there was no consequence of sEH inhibition on the formation of metastases in the lymph node or lung. Taken together, our results confirm previous reports of increased tumor growth in animals lacking sEH but fail to substantiate reports of enhanced lymph node or pulmonary metastases.
多不饱和脂肪酸 (PUFA) 的环氧化物和二醇是生物活性的，可影响肿瘤细胞增殖和血管生成等过程。在过表达细胞色素 P450 酶的动物中用可溶性环氧化物水解酶 (sEH) 的抑制剂进行的研究或在全身给予特定环氧化物后进行的研究表明，肿瘤转移的发生率明显增加。为了确定在自发性乳腺癌模型中 PUFA 环氧化物是否增加转移，将 sEH 小鼠与多瘤病毒中 T 抗原 (PyMT) 背景杂交。我们发现 sEH 的缺失加速了原发性肿瘤的生长，并增加了肿瘤巨噬细胞计数和血管生成。肿瘤中环氧化物/二醇的含量存在微小差异，特别是环氧十八碳一烯酸与二羟基十八碳烯酸之间，与细胞增殖和代谢相关的蛋白质表达也发生了显著变化。然而，sEH 抑制对淋巴结或肺部转移的形成没有影响。总之，我们的结果证实了先前关于缺乏 sEH 的动物肿瘤生长增加的报告，但未能证实淋巴结或肺部转移增强的报告。
