cdw17-antigen and Neoplasms

β-1,4-Galactosyltransferase (β-1,4-GalT) V - whose human and mouse genes were cloned by us - has been suggested to be involved in the biosyntheses of N-glycans, O-glycans, and lactosylceramide by in vitro studies. Our recent study showed that β-1,4-GalT V-knockout mice are embryonic lethal, suggesting the importance of the glycans synthesized by β-1,4-GalT V for embryonic development. A subsequent study showed that murine β-1,4-GalT V is involved in the biosynthesis of lactosylceramide. It is well known that the glycosylation of cell surface glycoproteins and glycolipids changes dramatically upon the malignant transformation of cells. We found that among six β-1,4-GalTs the gene expression of only β-1,4-GalT V increases upon malignant transformation. The expression of the β-1,4-GalT V gene has been shown to be regulated by transcription factors Sp1 and Ets-1 in cancer cells. Both transcription factors regulate the gene expression levels of not only glycosyltransferases, but also key molecules involved in tumor growth, invasion and metastasis. Therefore, the abnormal glycosylation and malignant phenotypes of cancer cells are considered to be suppressed by regulating the expression levels of the transcription factor genes. This review gives a summary account of the gene discovery, in vivo function, and transcriptional mechanism of β-1,4-GalT V. Also, a perspective on applications of the manipulation of transcription factor genes to cancer therapy will be discussed.

Topics: Animals; Antigens, CD; Cell Transformation, Neoplastic; Embryonic Development; Galactosyltransferases; Gene Expression Regulation, Neoplastic; Genetic Therapy; Glycolipids; Glycosylation; Humans; Lactosylceramides; Membrane Glycoproteins; Mice; Neoplasms; Polysaccharides; Proto-Oncogene Protein c-ets-1; Sp1 Transcription Factor; Transcription, Genetic

Monoclonal antibody KH2 (IgM) reactive with lactosyl ceramide and neolactotetraosyl ceramide was applied for the first time to the staining of human cancerous and noncancerous tissues which were fixed with formalin and embedded in paraffin. Digestive-tract cancers originating from stomach, colon, pancreas, gallbladder and bile duct were clearly stained. The staining intensity was especially strong in the apical portion and the intraluminal content of adenocarcinomas. In noncancerous tissues, it was of interest that gastric intestinal metaplasia and certain fetal tissues were stained. A part of the tubules of the kidney, pancreatic ductal cells, lung alveolar epithelial cells and polymorphonuclear leukocytes were stained in normal adult tissues in our study. Enhancement of the intensity of immunostaining by neuraminidase treatment indicated that most of the antigenic determinants should be sialylated and the antigenicity exposed after neuraminidase treatment in several kinds of cancerous and noncancerous tissues. These data suggest that the monoclonal antibody KH2 may be useful in the immunohistologic diagnosis of formalin-fixed human cancerous tissues.

Topics: Antibodies, Monoclonal; Antigens, CD; Antigens, Tumor-Associated, Carbohydrate; Carcinoma; Carcinoma, Hepatocellular; Colonic Neoplasms; Glycosphingolipids; Humans; Immunoenzyme Techniques; Lactosylceramides; Liver Neoplasms; Neoplasms; Neuraminidase; Stomach Neoplasms

Topics: Antigens, CD; Lactosylceramides; Lipids; Neoplasms; Spleen

Topics: Antigens; Antigens, CD; Carbohydrates; Lactosylceramides; Lipids; Neoplasms

Topics: Antigens, CD; Cardiolipins; Haptens; Immune Sera; Lactosylceramides; Lipids; Neoplasms; Oxidation-Reduction

Topics: Antigens; Antigens, CD; Carcinoma; Haptens; Humans; Lactosylceramides; Neoplasms