B4GALNT2 gene expression controls the biosynthesis of Sda and sialyl Lewis X antigens in healthy and cancer human gastrointestinal tract |
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| Affiliation: | 1. Structural and Functional Glycobiology Unit, UMR CNRS 8576, University Lille Nord de France, Lille1, 59655 Villeneuve d’Ascq, France;2. Department of Medicine Clinical and Experimental (DMCS), University of Insubria Medical School, Varese, Italy;3. Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy;1. Department of Rheumatology, Ren Ji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China;2. Department of Ultrasound, Ren Ji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China;1. Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska;2. School of Interdisciplinary Informatics, University of Nebraska at Omaha, Omaha, Nebraska;3. Department of Chemical and Biological Engineering, Clinical and Translational Research Center, University at Buffalo, The State University of New York, Buffalo, New York;4. Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma;5. Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska;6. Department of Biostatistics, College of Public Health, University of Nebraska Medical Center, Omaha, Nebraska;7. Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska;8. Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, Nebraska;1. Department of Gastroenteology and Hepatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China;2. Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China |
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| Abstract: | The histo blood group carbohydrate Sda antigen and its cognate biosynthetic enzyme B4GALNT2 show the highest level of expression in normal colon. Their dramatic down regulation previously observed in colon cancer tissues could play a role in the concomitant elevation of the selectin ligand sLex, involved in metastasis. However, down regulation of sLex expression by B4GALNT2 has been so far demonstrated in vitro, but not in tissues. The human B4GALNT2 gene specifies at least two transcripts, diverging in the first exon, never studied in normal and cancer tissues. The long form contains a 253 nt exon 1L; the short form contains a 38 nt exon 1S. Using qPCR, we showed that cell lines and normal or cancerous colon, expressed almost exclusively the short form, while the long form was mainly expressed by the embryonic colon fibroblast cell line CCD112CoN. Immunochemistry approaches using colon cancer cells permanently expressing either B4GALNT2 cDNAs as controls, led to the observation of several protein isoforms in human normal and cancerous colon, and cell lines. We showed that tissues expressing B4GALNT2 protein isoforms were able to induce Sda and to inhibit sLex expression; both of which are expressed mainly on PNGase F-insensitive carbohydrate chains. Concomitant expression of B4GALNT2 and siRNA-mediated inhibition of FUT6, the major fucosyltransferase involved in sLex synthesis in colon, resulted in a cumulative inhibition of sLex. In normal colon samples a significant relationship between sLex expression and the ratio between FUT6/B4GALNT2 activities exists, demonstrating for the first time a role for B4GALNT2 in sLex inhibition in vivo. |
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| Keywords: | Glycosylation Colon cancer B4GALNT2 Glycosyltransferases |
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