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.