Based on our previous analysis of neutral
glycolipids in the human endometrium, the present authors already reported that the concentrations of
glucosylceramide,
lactosylceramide and
globotriaosylceramide (
Gb3Cer), in which both
fatty acids and sphingosines in the
ceramides are hydroxylated, exhibit a marked increase during the luteal phase of the menstrual cycle. It is also well known that poorly differentiated endometrial
adenocarcinoma exhibits a more rapid progression and a worse response to
therapy than well-differentiated endometrial
adenocarcinoma. To examine the molecular background of well-differentiated and poorly differentiated
cancers, the levels of neutral
glycolipids in
tumor tissues from
endometrial carcinoma displaying different degrees of differentiation were measured. The composition of neutral
glycolipids in
tumor tissues was determined, and
ceramide structures that were specifically expressed in well-differentiated
endometrial carcinomas were investigated using biochemical analytical methods, including
lipid extraction,
enzyme digestion, thin-layer chromatography (TLC), gas-liquid chromatography and mass spectrometry. Well-differentiated
adenocarcinoma contained numerous structurally unknown
glycolipids that exhibited slower migration than
globotetraosylceramide (
Gb4Cer). In the case of
Gb3Cer, three bands appeared on TLC in well-differentiated
cancer, but only two bands appeared in the poorly-differentiated
cancer. This difference was associated with the
fatty acid composition of
ceramide, since non-hydroxy
fatty acids with ≥20
carbon atoms were increased in well-differentiated
cancer, while α-hydroxy
fatty acids were increased in poorly differentiated
cancer. Similarly, there were two bands on TLC of
Gb4Cer from well-differentiated
cancer, but only one band in poorly differentiated
cancer, and the long-chain base of
ceramide was observed to contain
phytosphingosine in well-differentiated
cancer. It was demonstrated in
endometrial cancer that the structure of
ceramide molecules changes with the extent of
tumor differentiation. These findings suggest that hydroxylated
ceramides contribute to the well-differentiated phenotype of endometrial
adenocarcinoma.