Abstract
This study was undertaken to investigate the kinetics and molecular requirements of platelet binding to tumor cells in bulk suspensions subjected to a uniform linear shear field, using a human colon adenocarcinoma cell line (LS174T) as a model. The effects of shear rate (20-1000 s(-1)), shear exposure time (30-300 s), shear stress (at constant shear rate by adjusting the viscosity of the medium from 1.3-2.6 cP), cell concentration, and platelet activation on platelet-LS174T heteroaggregation were assessed. The results indicate that hydrodynamic shear-induced collisions augment platelet-LS174T binding, which is further potentiated by thrombin/GPRP-NH(2). Peak adhesion efficiency occurs at low shear and decreases with increasing shear. Intercellular contact duration is the predominant factor limiting heteroaggregation at shear rates up to 200 s(-1), whereas these interactions become shear stress-sensitive at > or = 400 s(-1). Heteroaggregation increases with platelet concentration due to an elevation of the intercellular collision frequency, whereas adhesion efficiency remains nearly constant. Moreover, hydrodynamic shear affects the receptor specificity of activation-dependent platelet binding to LS174T cells, as evidenced by the transition from a P-selectin-independent/Arg-Gly-Asp (RGD)-dependent process at 100 s(-1) to a P-selectin/alpha(IIb)beta(3)-dependent interaction at 800 s(-1). This study demonstrates that platelet activation and a fluid-mechanical environment representative of the vasculature affect platelet-tumor cell adhesive interactions pertinent to the process of blood-borne metastasis.
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- Abulencia J. P., Tien N., McCarty O. J., Plymire D., Mousa S. A., Konstantopoulos K. Comparative antiplatelet efficacy of a novel, nonpeptide GPIIb/IIIa antagonist (XV454) and abciximab (c7E3) in flow models of thrombosis. Arterioscler Thromb Vasc Biol. 2001 Jan;21(1):149–156. doi: 10.1161/01.atv.21.1.149. [DOI] [PubMed] [Google Scholar]
- Biggerstaff J. P., Seth N., Amirkhosravi A., Amaya M., Fogarty S., Meyer T. V., Siddiqui F., Francis J. L. Soluble fibrin augments platelet/tumor cell adherence in vitro and in vivo, and enhances experimental metastasis. Clin Exp Metastasis. 1999;17(8):723–730. doi: 10.1023/a:1006763827882. [DOI] [PubMed] [Google Scholar]
- Bonnefoy A., Liu Q., Legrand C., Frojmovic M. M. Efficiency of platelet adhesion to fibrinogen depends on both cell activation and flow. Biophys J. 2000 Jun;78(6):2834–2843. doi: 10.1016/S0006-3495(00)76826-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Capon C., Wieruszeski J. M., Lemoine J., Byrd J. C., Leffler H., Kim Y. S. Sulfated lewis X determinants as a major structural motif in glycans from LS174T-HM7 human colon carcinoma mucin. J Biol Chem. 1997 Dec 19;272(51):31957–31968. doi: 10.1074/jbc.272.51.31957. [DOI] [PubMed] [Google Scholar]
- Chen S., Springer T. A. Selectin receptor-ligand bonds: Formation limited by shear rate and dissociation governed by the Bell model. Proc Natl Acad Sci U S A. 2001 Jan 30;98(3):950–955. doi: 10.1073/pnas.98.3.950. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Felding-Habermann B., Habermann R., Saldívar E., Ruggeri Z. M. Role of beta3 integrins in melanoma cell adhesion to activated platelets under flow. J Biol Chem. 1996 Mar 8;271(10):5892–5900. doi: 10.1074/jbc.271.10.5892. [DOI] [PubMed] [Google Scholar]
- Gasic G. J., Gasic T. B., Stewart C. C. Antimetastatic effects associated with platelet reduction. Proc Natl Acad Sci U S A. 1968 Sep;61(1):46–52. doi: 10.1073/pnas.61.1.46. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Goldsmith H. L., Frojmovic M. M., Braovac S., McIntosh F., Wong T. Adenosine diphosphate-induced aggregation of human platelets in flow through tubes: III. Shear and extrinsic fibrinogen-dependent effects. Thromb Haemost. 1994 Jan;71(1):78–90. [PubMed] [Google Scholar]
- Hardwick R. A., Hellums J. D., Moake J. L., Peterson D. M., Alfrey C. P. Effects of antiplatelet agents on platelets exposed to shear stress. Trans Am Soc Artif Intern Organs. 1980;26:179–184. [PubMed] [Google Scholar]
- Hentzen E. R., Neelamegham S., Kansas G. S., Benanti J. A., McIntire L. V., Smith C. W., Simon S. I. Sequential binding of CD11a/CD18 and CD11b/CD18 defines neutrophil capture and stable adhesion to intercellular adhesion molecule-1. Blood. 2000 Feb 1;95(3):911–920. [PubMed] [Google Scholar]
- Honn K. V., Tang D. G., Crissman J. D. Platelets and cancer metastasis: a causal relationship? Cancer Metastasis Rev. 1992 Nov;11(3-4):325–351. doi: 10.1007/BF01307186. [DOI] [PubMed] [Google Scholar]
- Huang P. Y., Hellums J. D. Aggregation and disaggregation kinetics of human blood platelets: Part II. Shear-induced platelet aggregation. Biophys J. 1993 Jul;65(1):344–353. doi: 10.1016/S0006-3495(93)81079-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Huber W., Hurst J., Schlatter D., Barner R., Hübscher J., Kouns W. C., Steiner B. Determination of kinetic constants for the interaction between the platelet glycoprotein IIb-IIIa and fibrinogen by means of surface plasmon resonance. Eur J Biochem. 1995 Feb 1;227(3):647–656. doi: 10.1111/j.1432-1033.1995.tb20184.x. [DOI] [PubMed] [Google Scholar]
- Jadhav S., Bochner B. S., Konstantopoulos K. Hydrodynamic shear regulates the kinetics and receptor specificity of polymorphonuclear leukocyte-colon carcinoma cell adhesive interactions. J Immunol. 2001 Nov 15;167(10):5986–5993. doi: 10.4049/jimmunol.167.10.5986. [DOI] [PubMed] [Google Scholar]
- Karpatkin S., Pearlstein E., Ambrogio C., Coller B. S. Role of adhesive proteins in platelet tumor interaction in vitro and metastasis formation in vivo. J Clin Invest. 1988 Apr;81(4):1012–1019. doi: 10.1172/JCI113411. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Konstantopoulos K., Kukreti S., McIntire L. V. Biomechanics of cell interactions in shear fields. Adv Drug Deliv Rev. 1998 Aug 3;33(1-2):141–164. doi: 10.1016/s0169-409x(98)00024-6. [DOI] [PubMed] [Google Scholar]
- Konstantopoulos K., Kukreti S., Smith C. W., McIntire L. V. Endothelial P-selectin and VCAM-1 each can function as primary adhesive mechanisms for T cells under conditions of flow. J Leukoc Biol. 1997 Feb;61(2):179–187. doi: 10.1002/jlb.61.2.179. [DOI] [PubMed] [Google Scholar]
- Konstantopoulos K., Neelamegham S., Burns A. R., Hentzen E., Kansas G. S., Snapp K. R., Berg E. L., Hellums J. D., Smith C. W., McIntire L. V. Venous levels of shear support neutrophil-platelet adhesion and neutrophil aggregation in blood via P-selectin and beta2-integrin. Circulation. 1998 Sep 1;98(9):873–882. doi: 10.1161/01.cir.98.9.873. [DOI] [PubMed] [Google Scholar]
- Laurenzi I. J., Diamond S. L. Monte Carlo simulation of the heterotypic aggregation kinetics of platelets and neutrophils. Biophys J. 1999 Sep;77(3):1733–1746. doi: 10.1016/S0006-3495(99)77019-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mannori G., Crottet P., Cecconi O., Hanasaki K., Aruffo A., Nelson R. M., Varki A., Bevilacqua M. P. Differential colon cancer cell adhesion to E-, P-, and L-selectin: role of mucin-type glycoproteins. Cancer Res. 1995 Oct 1;55(19):4425–4431. [PubMed] [Google Scholar]
- McCarty O. J., Mousa S. A., Bray P. F., Konstantopoulos K. Immobilized platelets support human colon carcinoma cell tethering, rolling, and firm adhesion under dynamic flow conditions. Blood. 2000 Sep 1;96(5):1789–1797. [PubMed] [Google Scholar]
- Nierodzik M. L., Klepfish A., Karpatkin S. Role of platelets, thrombin, integrin IIb-IIIa, fibronectin and von Willebrand factor on tumor adhesion in vitro and metastasis in vivo. Thromb Haemost. 1995 Jul;74(1):282–290. [PubMed] [Google Scholar]
- Nieswandt B., Hafner M., Echtenacher B., Männel D. N. Lysis of tumor cells by natural killer cells in mice is impeded by platelets. Cancer Res. 1999 Mar 15;59(6):1295–1300. [PubMed] [Google Scholar]
- Oleksowicz L., Mrowiec Z., Schwartz E., Khorshidi M., Dutcher J. P., Puszkin E. Characterization of tumor-induced platelet aggregation: the role of immunorelated GPIb and GPIIb/IIIa expression by MCF-7 breast cancer cells. Thromb Res. 1995 Aug 1;79(3):261–274. doi: 10.1016/0049-3848(95)00113-6. [DOI] [PubMed] [Google Scholar]
- Peng T. C., Kickler T. S., Bell W. R., Haller E. Obstetric complications in a patient with Bernard-Soulier syndrome. Am J Obstet Gynecol. 1991 Aug;165(2):425–426. doi: 10.1016/0002-9378(91)90110-d. [DOI] [PubMed] [Google Scholar]
- Pinedo H. M., Verheul H. M., D'Amato R. J., Folkman J. Involvement of platelets in tumour angiogenesis? Lancet. 1998 Nov 28;352(9142):1775–1777. doi: 10.1016/s0140-6736(98)05095-8. [DOI] [PubMed] [Google Scholar]
- Rinker K. D., Prabhakar V., Truskey G. A. Effect of contact time and force on monocyte adhesion to vascular endothelium. Biophys J. 2001 Apr;80(4):1722–1732. doi: 10.1016/S0006-3495(01)76143-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smith M. J., Berg E. L., Lawrence M. B. A direct comparison of selectin-mediated transient, adhesive events using high temporal resolution. Biophys J. 1999 Dec;77(6):3371–3383. doi: 10.1016/S0006-3495(99)77169-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Springer T. A. Traffic signals on endothelium for lymphocyte recirculation and leukocyte emigration. Annu Rev Physiol. 1995;57:827–872. doi: 10.1146/annurev.ph.57.030195.004143. [DOI] [PubMed] [Google Scholar]
- Stone J. P., Wagner D. D. P-selectin mediates adhesion of platelets to neuroblastoma and small cell lung cancer. J Clin Invest. 1993 Aug;92(2):804–813. doi: 10.1172/JCI116654. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Swift D. G., Posner R. G., Hammer D. A. Kinetics of adhesion of IgE-sensitized rat basophilic leukemia cells to surface-immobilized antigen in Couette flow. Biophys J. 1998 Nov;75(5):2597–2611. doi: 10.1016/S0006-3495(98)77705-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tandon P., Diamond S. L. Hydrodynamic effects and receptor interactions of platelets and their aggregates in linear shear flow. Biophys J. 1997 Nov;73(5):2819–2835. doi: 10.1016/S0006-3495(97)78311-5. [DOI] [PMC free article] [PubMed] [Google Scholar]