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Related Collections Hemostasis, Thrombosis, and Vascular Biology Neoplasia Cell Adhesion and Motility Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 September 2000, Vol. 96, No. 5, pp. 1789-1797 HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Immobilized platelets support human colon carcinoma cell tethering, rolling, and firm adhesion under dynamic flow conditions Owen J. T. McCarty, Shaker A. Mousa, Paul F. Bray, and Konstantinos Konstantopoulos From the Department of Chemical Engineering, Department of Medicine, Johns Hopkins University, Baltimore, MD; DuPont Pharmaceuticals Co, Wilmington, DE. Accumulating evidence suggests that successful metastatic spread may depend on the ability of tumor cells to undergo extensive interactions with platelets. However, the mechanisms mediating tumor cell adhesion to platelets under conditions of flow remain largely unknown. Therefore, this study was designed to analyze the ability of 3 human colon carcinoma cell lines (LS174T, COLO205, and HCT-8) to bind to surface-anchored platelets under flow and to identify the receptors involved in these processes. Immobilized platelets support LS174T cell adhesion at wall shear stresses up to 1.4 dyn/cm2. Our data suggest that platelets primarily recruit LS174T cells through a 2-step, sequential process of adhesive interactions that shares common features but is distinct from that elaborated for neutrophils. Platelet P-selectin mediates LS174T cell tethering and rolling in a PSGL-1- and CD24-independent manner. Moreover, platelet IIb3-integrins appear to be capable of directly capturing LS174T cells from the fluid stream, and also convert instantaneously transient tethers initiated by P-selectin into stable adhesion. This step is at least partially mediated by von Willebrand factor, but not fibrinogen or fibronectin, that bridges platelet IIb3 with a yet unidentified receptor on the LS174T cell surface via an RGD-dependent mechanism. The sequential engagement of platelet P-selectin and IIb3 is also requisite for the optimal adhesion of COLO205. Furthermore, HCT-8 cells, which fail to interact with P-selectin, tether minimally to surface-anchored platelets under flow, despite their extensive adhesive interactions under static conditions. This cascade of events depicts an efficacious process for colon carcinoma arrest at sites of vascular injury. © 2000 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. Nimrichter, M. M. Burdick, K. Aoki, W. Laroy, M. A. Fierro, S. A. Hudson, C. E. Von Seggern, R. J. Cotter, B. S. Bochner, M. Tiemeyer, et al. E-selectin receptors on human leukocytes Blood, November 1, 2008; 112(9): 3744 - 3752. [Abstract] [Full Text] [PDF] S. N. Thomas, F. Zhu, R. L. Schnaar, C. S. Alves, and K. Konstantopoulos Carcinoembryonic Antigen and CD44 Variant Isoforms Cooperate to Mediate Colon Carcinoma Cell Adhesion to E- and L-selectin in Shear Flow J. Biol. Chem., June 6, 2008; 283(23): 15647 - 15655. [Abstract] [Full Text] [PDF] C. S. Alves, M. M. Burdick, S. N. Thomas, P. Pawar, and K. Konstantopoulos The dual role of CD44 as a functional P-selectin ligand and fibrin receptor in colon carcinoma cell adhesion Am J Physiol Cell Physiol, April 1, 2008; 294(4): C907 - C916. [Abstract] [Full Text] [PDF] S. L. Napier, Z. R. Healy, R. L. Schnaar, and K. Konstantopoulos Selectin Ligand Expression Regulates the Initial Vascular Interactions of Colon Carcinoma Cells: THE ROLES OF CD44V AND ALTERNATIVE SIALOFUCOSYLATED SELECTIN LIGANDS J. Biol. Chem., February 9, 2007; 282(6): 3433 - 3441. [Abstract] [Full Text] [PDF] C. Medina, P. Jurasz, M. J. Santos-Martinez, S. S. Jeong, T. Mitsky, R. Chen, and M. W. Radomski Platelet Aggregation-Induced by Caco-2 Cells: Regulation by Matrix Metalloproteinase-2 and Adenosine Diphosphate J. Pharmacol. Exp. Ther., May 1, 2006; 317(2): 739 - 745. [Abstract] [Full Text] [PDF] L. H. K. Lim, M. M. Burdick, S. A. Hudson, F. B. Mustafa, K. Konstantopoulos, and B. S. Bochner Stimulation of Human Endothelium with IL-3 Induces Selective Basophil Accumulation In Vitro J. Immunol., May 1, 2006; 176(9): 5346 - 5353. [Abstract] [Full Text] [PDF] M. M. Burdick and K. Konstantopoulos Platelet-induced enhancement of LS174T colon carcinoma and THP-1 monocytoid cell adhesion to vascular endothelium under flow Am J Physiol Cell Physiol, August 1, 2004; 287(2): C539 - C547. [Abstract] [Full Text] [PDF] M. Wei, G. Tai, Y. Gao, N. Li, B. Huang, Y. Zhou, S. Hao, and X. Zeng Modified Heparin Inhibits P-selectin-mediated Cell Adhesion of Human Colon Carcinoma Cells to Immobilized Platelets under Dynamic Flow Conditions J. Biol. Chem., July 9, 2004; 279(28): 29202 - 29210. [Abstract] [Full Text] [PDF] O. J. T. McCarty, N. Tien, B. S. Bochner, and K. Konstantopoulos Exogenous eosinophil activation converts PSGL-1-dependent binding to CD18-dependent stable adhesion to platelets in shear flow Am J Physiol Cell Physiol, May 1, 2003; 284(5): C1223 - C1234. [Abstract] [Full Text] [PDF] M. M. Burdick, J. M. McCaffery, Y. S. Kim, B. S. Bochner, and K. Konstantopoulos Colon carcinoma cell glycolipids, integrins, and other glycoproteins mediate adhesion to HUVECs under flow Am J Physiol Cell Physiol, April 1, 2003; 284(4): C977 - C987. [Abstract] [Full Text] [PDF] W. Hanley, O. McCarty, S. Jadhav, Y. Tseng, D. Wirtz, and K. Konstantopoulos Single Molecule Characterization of P-selectin/Ligand Binding J. Biol. Chem., March 14, 2003; 278(12): 10556 - 10561. [Abstract] [Full Text] [PDF] S. K. Khaldoyanidi, V. V. Glinsky, L. Sikora, A. B. Glinskii, V. V. Mossine, T. P. Quinn, G. V. Glinsky, and P. Sriramarao MDA-MB-435 Human Breast Carcinoma Cell Homo- and Heterotypic Adhesion under Flow Conditions Is Mediated in Part by Thomsen-Friedenreich Antigen-Galectin-3 Interactions J. Biol. Chem., January 31, 2003; 278(6): 4127 - 4134. [Abstract] [Full Text] [PDF] S. Jadhav and K. Konstantopoulos Fluid shear- and time-dependent modulation of molecular interactions between PMNs and colon carcinomas Am J Physiol Cell Physiol, October 1, 2002; 283(4): C1133 - C1143. [Abstract] [Full Text] [PDF] O. J. T. McCarty, S. Jadhav, M. M. Burdick, W. R. Bell, and K. Konstantopoulos Fluid Shear Regulates the Kinetics and Molecular Mechanisms of Activation-Dependent Platelet Binding to Colon Carcinoma Cells Biophys. J., August 1, 2002; 83(2): 836 - 848. [Abstract] [Full Text] [PDF] J. Pilch, R. Habermann, and B. Felding-Habermann Unique Ability of Integrin alpha vbeta 3 to Support Tumor Cell Arrest under Dynamic Flow Conditions J. Biol. Chem., June 7, 2002; 277(24): 21930 - 21938. [Abstract] [Full Text] [PDF] M. Ikeda, H. Furukawa, H. Imamura, J. Shimizu, H. Ishida, S. Masutani, M. Tatsuta, and T. Satomi Poor Prognosis Associated With Thrombocytosis in Patients With Gastric Cancer Ann. Surg. Oncol., April 1, 2002; 9(3): 287 - 291. [Abstract] [Full Text] [PDF] S. Jadhav, B. S. Bochner, and K. Konstantopoulos Hydrodynamic Shear Regulates the Kinetics and Receptor Specificity of Polymorphonuclear Leukocyte-Colon Carcinoma Cell Adhesive Interactions J. Immunol., November 15, 2001; 167(10): 5986 - 5993. [Abstract] [Full Text] [PDF] J. P. Abulencia, N. Tien, O. J. T. McCarty, D. Plymire, S. A. Mousa, and K. Konstantopoulos Comparative Antiplatelet Efficacy of a Novel, Nonpeptide GPIIb/IIIa Antagonist (XV454) and Abciximab (c7E3) in Flow Models of Thrombosis Arterioscler. Thromb. Vasc. 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