Altered sphingolipid metabolism in human endometrial cancer

被引：55

作者：

Knapp, Pawel ^{[2
]}

Baranowski, Marcin ^{[1
]}

Knapp, Malgorzata ^{[3
]}

Zabielski, Piotr ^{[1
]}

Blachnio-Zabielska, Agnieszka U. ^{[1
]}

Gorski, Jan ^{[1
]}

机构：

[1] Med Univ Bialystok, Dept Physiol, PL-15222 Bialystok, Poland

[2] Med Univ Bialystok, Dept Gynecol, PL-15276 Bialystok, Poland

[3] Med Univ Bialystok, Dept Cardiol, PL-15276 Bialystok, Poland

来源：

PROSTAGLANDINS & OTHER LIPID MEDIATORS | 2010年 / 92卷 / 1-4期

关键词：

Endometrioid carcinoma; Tumor; Ceramide/S1P rheostat; SPT; SPHK; NOVO CERAMIDE SYNTHESIS; HUMAN COLON-CANCER; SPHINGOSINE KINASE; SERINE PALMITOYLTRANSFERASE; MALIGNANT-TUMORS; HUMAN HEAD; CELL; CARCINOMA; EXPRESSION; OVARY;

D O I：

10.1016/j.prostaglandins.2010.03.002

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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. (C) 2010 Elsevier Inc. All rights reserved.

引用

页码：62 / 66

页数：5

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