Department of Gynecology, Medical University of Białystok, Skłodowskiej-Curie 24A, 15-276 Białystok, Poland.
Prostaglandins Other Lipid Mediat. 2010 Jun;92(1-4):62-6. doi: 10.1016/j.prostaglandins.2010.03.002. Epub 2010 Mar 10.
There is a growing body of evidence indicating that bioactive sphingolipids play a key role in cancer development, progression and metastasis. However, sphingolipid metabolism in malignant tumors is poorly investigated. Therefore, the aim of the present study was to examine the content of selected intermediates of ceramide metabolism and the activity of key enzymes of ceramide de novo synthesis and sphingosine-1-phosphate (S1P) production in the endometrial cancer. The specimens of cancer tissue and healthy endometrium were obtained from women undergoing surgery because of the cancer (n=23) and because of myomas (n=18), respectively. The content of sphinganine, dihydroceramide, ceramide, sphingosine and S1P was measured using high pressure liquid chromatography. The activity of the enzymes was determined using radioactive substrates. It has been found that the content of each examined sphingolipid was markedly elevated in the cancer tissue compared with the healthy endometrium. Namely, sphinganine, sphingosine and dihydroceramide by 3-4.6-fold, ceramide and S1P by 1.9- and 1.6-fold, respectively. Interestingly, the ratio of S1P to ceramide remained stable. The activity of serine palmitoyltransferase and sphingosine kinase 1 was increased by 2.3- and 2.6-fold, respectively. We conclude that endometrial carcinoma is characterized by profound changes in sphingolipid metabolism that likely contribute to its progression and chemoresistance.
越来越多的证据表明，生物活性神经鞘脂在癌症的发生、发展和转移中起着关键作用。然而，恶性肿瘤中的神经鞘脂代谢研究甚少。因此，本研究旨在检测子宫内膜癌中神经酰胺代谢的某些中间产物的含量以及神经酰胺从头合成和鞘氨醇-1-磷酸（S1P）生成的关键酶的活性。分别从因癌症（n=23）和子宫肌瘤（n=18）而接受手术的女性中获取癌症组织和健康子宫内膜的标本。使用高压液相色谱法测量神经鞘氨醇、二氢神经酰胺、神经酰胺、鞘氨醇和 S1P 的含量。使用放射性底物测定酶的活性。研究发现，与健康子宫内膜相比，每种检查的神经鞘脂在癌症组织中的含量明显升高。具体而言，神经鞘氨醇、鞘氨醇和二氢神经酰胺分别增加了 3-4.6 倍、1.9-1.6 倍和 1.6 倍，而神经酰胺和 S1P 则分别增加了 1.9-1.6 倍和 1.6 倍。有趣的是，S1P 与神经酰胺的比值保持稳定。丝氨酸棕榈酰转移酶和鞘氨醇激酶 1 的活性分别增加了 2.3-2.6 倍。我们得出结论，子宫内膜癌的特征是神经鞘脂代谢发生深刻变化，这可能有助于其进展和化疗耐药性。
