This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Friederichs, J. Articles by Altevogt, P. Search for Related Content PubMed PubMed Citation Articles by Friederichs, J. Articles by Altevogt, P.

The CD24/P-selectin Binding Pathway Initiates Lung Arrest of Human A125 Adenocarcinoma Cells¹

Tumor Immunology Programme [J. F., Y. Z., P. A.] and Cellular and Molecular Pathology [H-J. G.], German Cancer Research Center, D-69120 Heidelberg, Germany, and Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia 22908 [A. H-M., K. L.]

Carbohydrates on tumor cells have been shown to play an important role in tumor metastasis. We demonstrated before that CD24, a M_r 35,000–60,000 mucine-type glycosylphosphatidylinositol-linked cell surface molecule, can function as ligand for P-selectin and that the sialylLe^x 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 sialylLe^x. Biochemical analysis confirmed that in A125-CD24/FucTVII double transfectants, CD24 was modified with sialylLe^x. 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 sialylLe^x 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 sialylLe^x but not CD24 did not show P-selectin-mediated lung arrest. The sialylLe^x epitope is abundantly expressed on human carcinomas, and significant correlations between sialylLe^x expression and clinical prognosis exist. Our data suggest an important role for sialylLe^x-modified CD24 in the lung colonization of human tumors.

This article has been cited by other articles:

				X.-R. Yang, Y. Xu, B. Yu, J. Zhou, J.-C. Li, S.-J. Qiu, Y.-H. Shi, X.-Y. Wang, Z. Dai, G.-M. Shi, et al. CD24 Is a Novel Predictor for Poor Prognosis of Hepatocellular Carcinoma after Surgery Clin. Cancer Res., September 1, 2009; 15(17): 5518 - 5527. [Abstract] [Full Text] [PDF]

				C. Ay, R. Simanek, R. Vormittag, D. Dunkler, G. Alguel, S. Koder, G. Kornek, C. Marosi, O. Wagner, C. Zielinski, et al. High plasma levels of soluble P-selectin are predictive of venous thromboembolism in cancer patients: results from the Vienna Cancer and Thrombosis Study (CATS) Blood, October 1, 2008; 112(7): 2703 - 2708. [Abstract] [Full Text] [PDF]

				M. Shimoda, G. Hashimoto, S. Mochizuki, E. Ikeda, N. Nagai, S. Ishida, and Y. Okada Binding of ADAM28 to P-selectin Glycoprotein Ligand-1 Enhances P-selectin-mediated Leukocyte Adhesion to Endothelial Cells J. Biol. Chem., August 31, 2007; 282(35): 25864 - 25874. [Abstract] [Full Text] [PDF]

				S. C. Smith, G. Oxford, Z. Wu, M. D. Nitz, M. Conaway, H. F. Frierson, G. Hampton, and D. Theodorescu The Metastasis-Associated Gene CD24 Is Regulated by Ral GTPase and Is a Mediator of Cell Proliferation and Survival in Human Cancer Cancer Res., February 15, 2006; 66(4): 1917 - 1922. [Abstract] [Full Text] [PDF]

				H. Schabath, S. Runz, S. Joumaa, and P. Altevogt CD24 affects CXCR4 function in pre-B lymphocytes and breast carcinoma cells J. Cell Sci., January 15, 2006; 119(2): 314 - 325. [Abstract] [Full Text] [PDF]

				P. Baumann, N. Cremers, F. Kroese, G. Orend, R. Chiquet-Ehrismann, T. Uede, H. Yagita, and J. P. Sleeman CD24 Expression Causes the Acquisition of Multiple Cellular Properties Associated with Tumor Growth and Metastasis Cancer Res., December 1, 2005; 65(23): 10783 - 10793. [Abstract] [Full Text] [PDF]

				J. L. Stevenson, S. H. Choi, and A. Varki Differential Metastasis Inhibition by Clinically Relevant Levels of Heparins--Correlation with Selectin Inhibition, Not Antithrombotic Activity Clin. Cancer Res., October 1, 2005; 11(19): 7003 - 7011. [Abstract] [Full Text] [PDF]

				R. Fiume, I. Faenza, A. Matteucci, A. Astolfi, M. Vitale, A. M. Martelli, and L. Cocco Nuclear Phospholipase C {beta}1 (PLC{beta}1) Affects CD24 Expression in Murine Erythroleukemia Cells J. Biol. Chem., June 24, 2005; 280(25): 24221 - 24226. [Abstract] [Full Text] [PDF]

				G. Kristiansen, K.-J. Winzer, E. Mayordomo, J. Bellach, K. Schluns, C. Denkert, E. Dahl, C. Pilarsky, P. Altevogt, H. Guski, et al. CD24 Expression Is a New Prognostic Marker in Breast Cancer Clin. Cancer Res., October 15, 2003; 9(13): 4906 - 4913. [Abstract] [Full Text] [PDF]

				G. Kristiansen, C. Denkert, K. Schluns, E. Dahl, C. Pilarsky, and S. Hauptmann CD24 Is Expressed in Ovarian Cancer and Is a New Independent Prognostic Marker of Patient Survival Am. J. Pathol., October 1, 2002; 161(4): 1215 - 1221. [Abstract] [Full Text] [PDF]

				J. Lesley, N. M. English, I. Gal, K. Mikecz, A. J. Day, and R. Hyman Hyaluronan Binding Properties of a CD44 Chimera Containing the Link Module of TSG-6 J. Biol. Chem., July 12, 2002; 277(29): 26600 - 26608. [Abstract] [Full Text] [PDF]