Depletion of β1,6-N-acetylglucosaminyltransferase reduces E-selectin binding capacity and migratory potential of human gastrointestinal adenocarcinoma cells
The commonly altered glycosylation of tumor cells is a hallmark of tumor progression and metastasis formation. One prominent example is the interaction of sialylated glycans at the tumor cell surface with endothelial (E)-selectin as an early event of an adhesion cascade that enables extravasation of...
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Elsevier
2025-01-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558624001246 |
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| author | Lisa Staffeldt Hanna Maar Julia Beimdiek Samuel Chambers Kristoffer Riecken Mark von Itzstein Falk F.R. Buettner Arun Everest-Dass Tobias Lange |
| author_facet | Lisa Staffeldt Hanna Maar Julia Beimdiek Samuel Chambers Kristoffer Riecken Mark von Itzstein Falk F.R. Buettner Arun Everest-Dass Tobias Lange |
| author_sort | Lisa Staffeldt |
| collection | DOAJ |
| description | The commonly altered glycosylation of tumor cells is a hallmark of tumor progression and metastasis formation. One prominent example is the interaction of sialylated glycans at the tumor cell surface with endothelial (E)-selectin as an early event of an adhesion cascade that enables extravasation of circulating tumor cells (CTCs) into distant tissues. In a previous study, we identified GCNT3 (mucin-type core2/ core4 β1,6-N-acetylglucosaminyltransferase) highly over-expressed in gastrointestinal adenocarcinoma cells that facilitate the canonical E-selectin ligands sialyl-Lewis A and X (sLeA/X) for E-selectin binding and endothelial adhesion. Here we show that shRNA-mediated, stable depletion of GCNT3 reduced sLeA (tumor marker CA19-9) presentation on two out of three tested human gastrointestinal adenocarcinoma cell lines, concurrently showing reduced static E-selectin binding. Significant effects of GCNT3 depletion on dynamic, shear-resistant tumor cell adhesion on immobilized E-selectin as well as endothelial cells were only partially and inconsistently observable as were effects on tumor cell proliferation (2D) or 3D colony formation. Nevertheless, tumor cell migration was consistently reduced upon GCNT3 depletion in all tested cell lines. Detailed glycome analyses revealed that GCNT3 depletion caused cell line-specific alterations in N- and O-glycans as well as glycosphingolipids, collectively mainly associating with decreased Core-2 structures resulting in varied abundance of sialylation and Lewis antigen with consistent phenotypic changes. Distinctive N- and O-glycosylation features were found to be inherent to specific cell types. These findings suggest GCNT3 products as possible carriers of sLeA and static E-selectin binding sites as well as common pro-migratory glycans in human gastrointestinal cancer. |
| format | Article |
| id | doaj-art-ef40da9ca4364521a9d375bdd0324fd3 |
| institution | Kabale University |
| issn | 1476-5586 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj-art-ef40da9ca4364521a9d375bdd0324fd32024-12-17T04:59:01ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55862025-01-0159101083Depletion of β1,6-N-acetylglucosaminyltransferase reduces E-selectin binding capacity and migratory potential of human gastrointestinal adenocarcinoma cellsLisa Staffeldt0Hanna Maar1Julia Beimdiek2Samuel Chambers3Kristoffer Riecken4Mark von Itzstein5Falk F.R. Buettner6Arun Everest-Dass7Tobias Lange8Institute of Anatomy and Experimental Morphology, University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, 20241, Hamburg, GermanyInstitute of Anatomy and Experimental Morphology, University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, 20241, Hamburg, Germany; Institute of Anatomy I, Jena University Hospital, 07743, Jena, Germany; Comprehensive Cancer Center Central Germany (CCCG)Institute of Clinical Biochemistry, Hannover Medical School, 30625, Hannover, Germany; Proteomics, Institute of Theoretical Medicine, Faculty of Medicine, University of Augsburg, Augsburg, GermanyInstitute for Glycomics, Griffith University, Gold Coast Campus, Gold Coast, QLD4222, AustraliaResearch Department Cell and Gene Therapy, Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, 20246, HamburgInstitute for Glycomics, Griffith University, Gold Coast Campus, Gold Coast, QLD4222, AustraliaInstitute of Anatomy and Experimental Morphology, University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, 20241, Hamburg, Germany; Institute of Clinical Biochemistry, Hannover Medical School, 30625, Hannover, Germany; Proteomics, Institute of Theoretical Medicine, Faculty of Medicine, University of Augsburg, Augsburg, GermanyInstitute of Anatomy and Experimental Morphology, University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, 20241, Hamburg, Germany; Institute for Glycomics, Griffith University, Gold Coast Campus, Gold Coast, QLD4222, AustraliaInstitute of Anatomy and Experimental Morphology, University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, 20241, Hamburg, Germany; Institute of Anatomy I, Jena University Hospital, 07743, Jena, Germany; Comprehensive Cancer Center Central Germany (CCCG); Corresponding author.The commonly altered glycosylation of tumor cells is a hallmark of tumor progression and metastasis formation. One prominent example is the interaction of sialylated glycans at the tumor cell surface with endothelial (E)-selectin as an early event of an adhesion cascade that enables extravasation of circulating tumor cells (CTCs) into distant tissues. In a previous study, we identified GCNT3 (mucin-type core2/ core4 β1,6-N-acetylglucosaminyltransferase) highly over-expressed in gastrointestinal adenocarcinoma cells that facilitate the canonical E-selectin ligands sialyl-Lewis A and X (sLeA/X) for E-selectin binding and endothelial adhesion. Here we show that shRNA-mediated, stable depletion of GCNT3 reduced sLeA (tumor marker CA19-9) presentation on two out of three tested human gastrointestinal adenocarcinoma cell lines, concurrently showing reduced static E-selectin binding. Significant effects of GCNT3 depletion on dynamic, shear-resistant tumor cell adhesion on immobilized E-selectin as well as endothelial cells were only partially and inconsistently observable as were effects on tumor cell proliferation (2D) or 3D colony formation. Nevertheless, tumor cell migration was consistently reduced upon GCNT3 depletion in all tested cell lines. Detailed glycome analyses revealed that GCNT3 depletion caused cell line-specific alterations in N- and O-glycans as well as glycosphingolipids, collectively mainly associating with decreased Core-2 structures resulting in varied abundance of sialylation and Lewis antigen with consistent phenotypic changes. Distinctive N- and O-glycosylation features were found to be inherent to specific cell types. These findings suggest GCNT3 products as possible carriers of sLeA and static E-selectin binding sites as well as common pro-migratory glycans in human gastrointestinal cancer.http://www.sciencedirect.com/science/article/pii/S1476558624001246β1,6-N-acetylglucosaminyltransferaseGCNT3Gastrointestinal adenocarcinomaE-selectinSialyl-Lewis ATumor cell migration |
| spellingShingle | Lisa Staffeldt Hanna Maar Julia Beimdiek Samuel Chambers Kristoffer Riecken Mark von Itzstein Falk F.R. Buettner Arun Everest-Dass Tobias Lange Depletion of β1,6-N-acetylglucosaminyltransferase reduces E-selectin binding capacity and migratory potential of human gastrointestinal adenocarcinoma cells Neoplasia: An International Journal for Oncology Research β1,6-N-acetylglucosaminyltransferase GCNT3 Gastrointestinal adenocarcinoma E-selectin Sialyl-Lewis A Tumor cell migration |
| title | Depletion of β1,6-N-acetylglucosaminyltransferase reduces E-selectin binding capacity and migratory potential of human gastrointestinal adenocarcinoma cells |
| title_full | Depletion of β1,6-N-acetylglucosaminyltransferase reduces E-selectin binding capacity and migratory potential of human gastrointestinal adenocarcinoma cells |
| title_fullStr | Depletion of β1,6-N-acetylglucosaminyltransferase reduces E-selectin binding capacity and migratory potential of human gastrointestinal adenocarcinoma cells |
| title_full_unstemmed | Depletion of β1,6-N-acetylglucosaminyltransferase reduces E-selectin binding capacity and migratory potential of human gastrointestinal adenocarcinoma cells |
| title_short | Depletion of β1,6-N-acetylglucosaminyltransferase reduces E-selectin binding capacity and migratory potential of human gastrointestinal adenocarcinoma cells |
| title_sort | depletion of β1 6 n acetylglucosaminyltransferase reduces e selectin binding capacity and migratory potential of human gastrointestinal adenocarcinoma cells |
| topic | β1,6-N-acetylglucosaminyltransferase GCNT3 Gastrointestinal adenocarcinoma E-selectin Sialyl-Lewis A Tumor cell migration |
| url | http://www.sciencedirect.com/science/article/pii/S1476558624001246 |
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