i(3)so3-galactosylceramide and Adenocarcinoma

It is well known that a poorly differentiated endometrial adenocarcinoma shows more rapid progression and a worse response to therapy than a well-differentiated endometrial adenocarcinoma. Qualitative and quantitative changes of cell surface glycolipids occur during neoplastic transformation. Sulfatide is one of the sulfated glycolipids in the cell membrane that may have an important role in various functions such as cell adhesion. To examine the molecular background of the morphological and biological features of well-differentiated and poorly differentiated cancer, we measured the levels of lipids, especially glycolipids, in tumor tissues from patients with endometrial carcinoma.. We determined the composition of lipids and glycolipids in tumor tissues, investigated glycosyltransferase messenger RNA expression by the reverse transcription-polymerase chain reaction, and assessed the localization of galactosylceramide sulfotransferase (an enzyme involved in sulfatide biosynthesis) by immunohistochemical staining.. No significant differences were observed between well-differentiated and poorly differentiated cancer with respect to the levels of cholesterol ester, cholesterol, phospholipids, cholesterol sulfate, ceramides, neutral glycolipids of the globo series, and GM3 ganglioside. However, the amount of sulfatides in well-differentiated tumors was significantly greater than that in poorly differentiated tumors, which was confirmed by thin-layer chromatography and immunostaining with a monoclonal antisulfatide antibody. Altered expression of sulfatide was found to be secondary to a change of galactosylceramide sulfotransferase messenger RNA expression. Immunohistochemical staining revealed that galactosylceramide sulfotransferase expression was characteristically observed in glandular areas but not in solid areas.. These findings suggest that sulfatide contributes to the well-differentiated phenotype of endometrial adenocarcinoma and that it is being expressed in normal uterine endometrium at sites of gland formation during the luteal phase, as we have previously reported.

Topics: Adenocarcinoma; Cell Differentiation; Chromatography, Thin Layer; Endometrial Neoplasms; Female; Humans; Immunoenzyme Techniques; Neoplasm Grading; Prognosis; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sulfoglycosphingolipids; Sulfotransferases

A biochemical study of sulfatides and arylsulfatase A (ASA) was carried out in the submandibular and sublingual glands of the male and female hamster Mesocricetus auratus after experimental induction of oral adenocarcinoma by 7,12-dimethylbenzanthracene (DMBA). Hamster experimental groups included control animals, animals treated with beta-carotene, animals treated with DMBA, and animals treated with DMBA plus beta-carotene. Oral cavity treatment with DMBA induced carcinogenesis in the buccal mucosa, but not in the major salivary glands, where nevertheless, the morphology and expression of both parameters examined changed. In fact, sulfatide concentrations and enzyme activity increased significantly, while in control and beta-carotene-treated hamsters they were similar in both glands and sexes. After administration of DMBA plus beta-carotene, sulfatide concentration decreased, as did ASA activity, slightly in the submandibular gland and remarkably so in the sublingual one of female hamsters. Thin-layer chromatography (TLC) analysis of lipid patterns, after DMBA treatment, revealed considerable differences, not only in sulfatides, but also in other lipid fractions, as well as between the two glands and two sexes. These findings show that oral cavity treatment with DMBA is not able to induce carcinogenesis in the major salivary glands examined; however, it does cause considerable metabolic changes.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Adenocarcinoma; Animals; Carcinogens; Cerebroside-Sulfatase; Cricetinae; Female; Lipid Metabolism; Male; Mouth; Mouth Neoplasms; Salivary Glands; Sex Factors; Sulfoglycosphingolipids; Tissue Distribution

Immunohistochemical staining using a specific monoclonal antibody against sulfatide was performed to examine cellular localization of sulfatides in normal human gastric mucosa and in various types of gastric carcinoma. In normal gastric mucosa without Helicobacter pylori infection, both epithelial and glandular cells were densely stained with anti-sulfatide antibody. Sulfatide staining was more abundant in the apical area of normal epithelium compared with cytosol or basolateral areas. This tendency was stronger in the antrum than the gastric body and was more intensified in glandular cells of the pyloric glands. The levels of sulfatide expression were decreased in papillary and well-differentiated adenocarcinomas compared with normal mucosa, were markedly attenuated in moderately differentiated adenocarcinomas, and were very low in poorly differentiated adenocarcinomas. The polarity of the stains was preserved in gastric cancers that exhibited differentiated tissue organization. The levels of sulfatide expression were highly variable in signet ring carcinoma cells. The cancer cells that expressed sulfatides did not show any polarity of staining.

Topics: Adenocarcinoma; Adenocarcinoma, Papillary; Adolescent; Adult; Aged; Aged, 80 and over; Carcinoma, Signet Ring Cell; Female; Gastric Mucosa; Humans; Immunohistochemistry; Male; Middle Aged; Stomach Neoplasms; Sulfoglycosphingolipids

Lactosylceramide sulfate and galactosylceramide sulfate were found to increase markedly in human renal cell carcinoma (adenocarcinoma) as compared to uninvolved tissue. Activities of two sulfotransferases toward galactosylceramide and lactosylceramide as substrates were significantly elevated in the carcinoma compared to the uninvolved tissue resulting in enhanced synthesis of the two sulfatides in the carcinoma. The elevation of the two sulfotransferases was parallel in most tumors, suggesting that the same enzyme is responsible for the enhanced synthesis of two sulfatides. No consistent difference in the activity of arylsulfatase A, which desulfates the two sulfatides, was observed between the carcinoma and uninvolved tissue. Both the present and previous results show that the increased synthesis of the sulfatide(s) due to elevated sulfotransferase activity could be a biochemical characteristic common to adenocarcinomas derived from different tissues.

Topics: Adenocarcinoma; Adult; Aged; Antigens, CD; Carcinoma, Renal Cell; Cerebroside-Sulfatase; Female; Galactosylceramides; Glycosphingolipids; Humans; Kidney Neoplasms; Lactosylceramides; Male; Middle Aged; Sulfoglycosphingolipids; Sulfurtransferases

Sulfatide-containing liposomes composed of PC, cholesterol, and sulfatide in a molar ratio of 7:2:1 entrapped ADM most efficiently among the negatively-charged liposomes tested. A unilamellar vesicle entrapped 123 ADM molecules, of which 6 molecules are localized in the internal space of the vesicle, 4 molecules are embedded into the membrane matrix, and 113 molecules are bound to the inner surface of the liposomal membrane. Highly efficient entrapment of ADM by the liposomes seems to be due to their rigidity. By the experiment using ovarian tumor-bearing nude mice, it was found that the liposome-entrapped ADM was maintained at much higher blood level, at lower concentration in the heart, and at higher concentration in the tumor than the free drug. The antitumor activity of the liposome-entrapped ADM was comparable with that of the free drug. The body weight of the animals was not affected by the former, whereas it was drastically decreased by the latter.

Topics: Adenocarcinoma; Animals; Doxorubicin; Drug Carriers; Endometriosis; Female; Liposomes; Mice; Mice, Nude; Neoplasm Transplantation; Ovarian Neoplasms; Sulfoglycosphingolipids

Glycosphingolipids, which have recently attracted attention due to their biological significance in cell membrane, human uterine endometrium and endometrial cancer cell lines were analyzed biochemically. Among the neutral and acidic glycosphingolipids in uterine endometrium, the concentration of sulfatide, I3Sulfo-GalCer, significantly increased 16-fold from the proliferative to the secretory phases of the menstrual cycle, suggesting that sex steroid hormones induce sulfotransferase, which is responsible for the synthesis of sulfatide. On the other hand, SNG-II and SNG-M derived from endometrial adenocarcinoma showed a predominant synthetic capacity for I3Sulfo-LacCer and II3Sulfo-Gg3Cer. The apparent Km of cerebroside sulfotransferase in SNG-II was about 60 microM, whereas gynecological cancer cell lines established from different regions of the tumor did not show a synthetic capacity for sulfoglycolipids. The present study suggested that sulfoglycolipids are closely related to the cell function of uterine endometrium in association with sex steroid hormones, and that endometrial cancer cell lines are useful in investigating the biological functions of sulfoglycolipids.

Topics: Adenocarcinoma; Endometrium; Female; Glycolipids; Glycosphingolipids; Humans; Menstrual Cycle; Sulfoglycosphingolipids; Sulfotransferases; Tumor Cells, Cultured; Uterine Neoplasms

Human lung carcinoma tissues with histological types of adenocarcinoma, squamous cell and small cell undifferentiated carcinomas were investigated for glycolipids. Carcinoma tissues, as well as normal adult and embryonic lungs contained ceramide mono-, di- and trihexosides, globoside and hematoside as major glycolipids. In addition to them, sulfatide which was identified as ceramide 3-sulfate-galactoside, was isolated in much lesser amount. The content of sulfatide was markedly increased in adenocarcinoma than that in other carcinomas and normal lung. Adenocarcinoma was also characterized by significantly lower level of total glycolipids which was largely due to the diminished contents of ceramide mono- and dihexosides, and hematoside, as compared to those in other two carcinomas. Squamous cell carcinoma had a characteristic pattern with an increment of hematoside. In small cell undifferentiated carcinoma, glycolipid contents were similar with those in squamous cell carcinoma but the relative composition of major glycolipids was markedly differed from that in other types. All the types of carcinoma examined showed marked increase of ceramide mono- and dihexosides (except for ceramide dihexoside in adenocarcinoma) compared to those in normal adult lung. Overall feature of glycolipids in embryonic lung appeared to be an intermediate between carcinomas and normal adult lung.

Topics: Adenocarcinoma; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Female; G(M3) Ganglioside; Globosides; Glycosphingolipids; Humans; Lung; Lung Neoplasms; Pregnancy; Sulfoglycosphingolipids; Trihexosylceramides