title: The CD24/P-selectin binding pathway initiates lung arrest of human A125 adenocarcinoma cells.
abstract: Carbohydrates on tumor cells have been shown to play an important role in tumor metastasis. We demonstrated before that CD24, a Mr 35,000-60,000 mucine-type glycosylphosphatidylinositol-linked cell surface molecule, can function as ligand for P-selectin and that the sialylLex carbohydrate is essential for CD24-mediated rolling of tumor cells on P-selectin. To investigate the role of both antigens more closely, we transfected human A125 adenocarcinoma cells with CD24 and/or fucosyltransferase VII (Fuc TVII) cDNAs. Stable transfectants expressed CD24 and/or sialylLex. Biochemical analysis confirmed that in A125-CD24/FucTVII double transfectants, CD24 was modified with sialylLex. Only double transfectants showed rolling on P-selectin in vivo. When injected into mice, double transfectants arrested in the lungs, and this step was P-selectin dependent because it was strongly enhanced in lipopolysaccharide (LPS) pretreated wild-type mice but not in P-selectin knockout mice. CD24 modified by sialylLex was required on the tumor cells because the LPS-induced lung arrest was abolished by removal of CD24 from the cell surface by phosphatidylinositol-specific phospholipase C. A125-FucTVII single transfectants expressing sialylLex but not CD24 did not show P-selectin-mediated lung arrest. The sialylLex epitope is abundantly expressed on human carcinomas, and significant correlations between sialylLex expression and clinical prognosis exist. Our data suggest an important role for sialylLex-modified CD24 in the lung colonization of human tumors.
authors: Tumor Immunology Programme, German Cancer Research Center, Heidelberg.
authors: J
authors: J
authors: Friederichs
authors: Y
authors: Y
authors: Zeller
authors: A
authors: A
authors: Hafezi-Moghadam
authors: H J
authors: HJ
authors: Gröne
authors: K
authors: K
authors: Ley
authors: P
authors: P
authors: Altevogt
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000473:pathology / Q000556:secondary*; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D001792:Blood Platelets / Q000378:metabolism; D051927:CD24 Antigen; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D005260:Female; D005647:Fucosyltransferases / Q000096:biosynthesis / Q000235:genetics; D006031:Glycosylation; D006801:Humans; D008168:Lung / Q000098:blood supply; D008175:Lung Neoplasms / Q000276:immunology / Q000473:pathology / Q000556:secondary*; D008297:Male; D008562:Membrane Glycoproteins; D051379:Mice; D008810:Mice, Inbred C57BL; D009844:Oligosaccharides / Q000378:metabolism / Q000502:physiology; D019007:P-Selectin / Q000097:blood / Q000378:metabolism / Q000502:physiology*; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D054801:Phosphoinositide Phospholipase C; D000080506:Sialyl Lewis X Antigen; D015398:Signal Transduction / Q000502:physiology; D014162:Transfection; D010738:Type C Phospholipases / Q000494:pharmacology
chemical_list: D015703:Antigens, CD; D051927:CD24 Antigen; C497889:CD24 protein, human; C497890:Cd24a protein, mouse; D008562:Membrane Glycoproteins; D009844:Oligosaccharides; D019007:P-Selectin; D000080506:Sialyl Lewis X Antigen; D005647:Fucosyltransferases; C031692:galactoside 3-fucosyltransferase; D010738:Type C Phospholipases; D054801:Phosphoinositide Phospholipase C; D043265:Phosphatidylinositol Diacylglycerol-Lyase