Abstract
This investigation explored how exercise intensity impacts platelet-mediated interactions of nasopharyngeal carcinoma cells (NPCs) and vascular endothelial cells (ECs) under shear flow in 33 males. Our results showed that (a) platelet–NPC aggregates (PNA) were associated with higher shear-induced P-selectin expression and glycoprotein αIIβ3 activation than platelet–platelet aggregates (PPA); (b) strenuous exercise (SE, up to \( \dot{V}{\text{O}}_{{2{ \max }}} \)), but not moderate exercise (ME, 60%\( \dot{V}{\text{O}}_{{2{ \max }}} \) for 30 min), increased both PPA and PNA in mimicked venous and arterial circuits and enhanced PNA in mimicked flow of stenotic vessels; (c) the percentages of PNA that remained bound to ECs in mimicked flow of post-capillary venules increased, while platelet-induced CD44 cleavage on NPC and trans-endothelial migration of NPC were enhanced following SE, but were unchanged in response to ME. We conclude that SE, but not ME, enhances the capacity of PNA to adhere to ECs, withstand flowing blood, and facilitate the invasion of NPCs toward ECs.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Aleviadrou BR, McIntire LV (1995) Rheology. In: Loscalzo J, Schafer AL (eds) Thrombosis and hemorrhage. Blackwell Science, Cambridge, pp 369–384
Ambrogi V, Pompeo E, Elia S et al (2003) The impact of cardiovascular comorbidity on the outcome of surgery for stage I and II non-small-cell lung cancer. Eur J Cardiothorac Surg 23:811–817. doi:10.1016/S1010-7940(03)00093-9
Borsig L (2004) Selectins facilitate carcinoma metastasis and heparin can prevent them. News Physiol Sci 19:16–21. doi:10.1152/nips.01450.2003
Bourguignon LYW, Gunja-Smith Z, Iida N et al (1998) CD44v3, 8–10 is involved in cytoskeleton-mediated tumor cell migration and matrix metalloproteinase (MMP-9) association in metastatic breast cancer cells. J Cell Physiol 176:206–215. doi:10.1002/(SICI)1097-4652(199807)176:1<206::AID-JCP22>3.0.CO;2-3
Burdick MM, Konstantopoulos K (2004) Platelet-induced enhancement of LS174T colon carcinoma and THP-1 monocytoid cell adhesion to vascular endothelial under flow. Am J Physiol 287:C539–C547. doi:10.1152/ajpcell.00450.2003
Davis JM, Kohut ML, Jackson DA et al (1998) Exercise effects on lung tumor metastases and in vitro alveolar macrophage antitumor cytotoxicity. Am J Physiol 274:R1454–R1459
Dohadwala M, Batra RK, Luo J et al (2002) Autocrine/paracrine prostaglandin E2 production by non-small cell lung cancer cells regulates matrix metalloproteinase-2 and CD44 in cyclooxygenase-2-dependent invasion. J Biol Chem 27:50828–50833. doi:10.1074/jbc.M210707200
Felding-Habermann B (2003) Targeting tumor cell–platelet interaction in breast cancer metastasis. Pathophysiol Haemost Thromb 33:56–58. doi:10.1159/000073295
Ferlay J, Bray F, Pisani P (2001) Cancer incidence, mortality and prevalence worldwide, version 1.0 (IARC Cancer Base No 5). IARC Press, Lyon
Geho DH, Bandle RW, Clair T et al (2005) Physiological mechanisms of tumor–cell invasion and migration. Physiology (Bethesda) 20:194–200. doi:10.1152/physiol.00009.2005
Goebeler M, Kaufmann D, Bröcker EB et al (1996) Migration of highly aggressive melanoma cells on hyaluronic acid is associated with functional changes, increased turnover and shedding of CD44 receptors. J Cell Biol 109:1957–1964
Grossi IM, Hatfield JS, Fitzgerald LA et al (1988) Role of tumor cell glycoproteins immunologically related to glycoproteins Ib and IIb/IIIa in tumor cell–platelet and tumor cell–matrix interactions. FASEB J 2:2385–2395
Huang GW, Nong HT, Nakamura M et al (1994) Enhancement of platelet aggregation in patients with nasopharyngeal carcinoma. Auris Nasus Larynx 21:173–177
Jaffe EA, Nachman RL, Becker CG et al (1973) Culture of human endothelial cells derived from umbilical veins: identification by morphologic and immunologic criteria. J Clin Invest 52:2745–2756. doi:10.1172/JCI107470
Jurasz P, Sawicki G, Duszyk M et al (2001) Matrix metalloproteinase 2 in tumor cell-induced platelet aggregation: regulation by nitric oxide. Cancer Res 61:376–382
Kajita M, Itoh Y, Mori H et al (2001) Membrane-type 1 matrix metalloproteinase cleaves CD44 and promotes cell migration. J Cell Biol 153:893–904. doi:10.1083/jcb.153.5.893
Keese CR, Bhawe K, Wegner J et al (2002) Real-time impedance assay to follow the invasive activities of metastatic cells in culture. Biotechniques 33:842–850
Kitagawa H, Yamamoto N, Yamamoto K et al (1989) Involvement of platelet membrane glycoprotein Ib and glycoprotein IIb/IIIa complex in thrombin-dependent and -independent platelet aggregations induced by tumor cells. Cancer Res 49:537–541
Lawler K, Meade G, O’Sullivan G et al (2004) Shear stress modulates the interaction of platelet-secreted matrix proteins with tumor cells through the integrin αvβ3. Am J Physiol Cell Physiol 287:C1320–C1327. doi:10.1152/ajpcell.00159.2004
Lee KW, Lip GYH (2004) Acute versus habitual exercise, thrombogenesis and exercise intensity. Thromb Haemost 91:416–419
Lin CT, Wong CI, Chan WY (1990) Establishment and characterization of two nasopharyngeal carcinoma cell lines. Lab Invest 62:713–724
Lindenmeyer F, Legrand Y, Menashi S (1997) Upregulation of MMP-9 expression in MDA-MB231 tumor cells by platelet granular membrane. FESEB Lett 418:19–22. doi:10.1016/S0014-5793(97)01336-7
Lo KW, To KF, Huang DP (2004) Focus on nasopharyngeal carcinoma. Cancer Cell 5:423–428. doi:10.1016/S1535-6108(04)00119-9
McCarty OJT, Jadhav S, Burdick MM et al (2002) Fluid shear regulates the kinetics and molecular mechanisms of activation-dependent platelet binding to colon carcinoma cells. Biophys J 83:836–848
Nierodzik ML, Plotkin A, Kajumo F et al (1991) Thrombin stimulates tumor–platelet adhesion in vitro and metastasis in vivo. J Clin Invest 87:229–236. doi:10.1172/JCI114976
Okamoto I, Kawano Y, Tsuiki H et al (1999) CD 44 cleavage induced by a membrane-associated metalloprotease plays a critical role in tumor cell migration. Oncogene 18:1435–1446. doi:10.1038/sj.onc.1202447
Oliveria SA, Christos PJ (1997) The epidemiology of physical activity and cancer. Ann N Y Acad Sci 833:79–90. doi:10.1111/j.1749-6632.1997.tb48595.x
Radak Z, Gaal D, Taylor AW et al (2002) Attenuation of the development of murine solid leukemia tumor by physical exercise. Antioxid Redox Signal 4:213–219. doi:10.1089/152308602753625979
Seiter S, Arch R, Reber S et al (1993) Prevention of tumor metastasis formation by anti-variant CD44. J Exp Med 177:443–455. doi:10.1084/jem.177.2.443
Theilmeier G, Lenaerts T, Remacle C et al (1999) Circulating activated platelets assist THP-1 monocytoid/endothelial cell interaction under shear stress. Blood 94:2725–2734
Tiruppathi C, Malik AB, Del Vecchio PJ et al (1992) Electrical method for detection of endothelial cell shape change in real time: assessment of endothelial barrier function. Proc Natl Acad Sci USA 89:7919–7923. doi:10.1073/pnas.89.17.7919
Tozzi-Ciancarelli MG, Penco M, Di Massimo C (2002) Influence of acute exercise on human platelet responsiveness: possible involvement of exercise-induced oxidative stress. Eur J Appl Physiol 86:266–272. doi:10.1007/s00421-001-0542-8
Trikha M, Zhou Z, Timar J et al (2002) Multiple roles for platelet GPIIb/IIIa and αvβ3 integrins in tumor growth, angiogenesis, and metastasis. Cancer Res 62:2824–2833
Tzanakakis GN, Agarwal K, Veronikis DK et al (1991) Effects of antiplatelet agents alone or in combinations on platelet aggregation and on liver metastases from a human pancreatic adenocarcinoma in the nude mouse. J Surg Oncol 48:45–50. doi:10.1002/jso.2930480109
Wang JS (2004) Intense exercise increases shear-induced platelet aggregation in men through enhancement of von Willebrand factor binding, glycoprotein IIb/IIIa activation, and P-selectin expression on platelets. Eur J Appl Physiol 91:741–747. doi:10.1007/s00421-004-1050-4
Wang JS (2006) Exercise prescription and thrombogenesis. J Biomed Sci 13:753–761. doi:10.1007/s11373-006-9105-7
Wang JS, Cheng LJ (1999) Effect of strenuous, acute exercise on α2-adrenergic agonist-potentiated platelet activation. Arterioscler Thromb Vasc Biol 19:1559–1565
Wang JS, Chow SE, Chen J-K (2003) Strenuous, acute exercise affects reciprocal modulation of platelet and polymorphonuclear leukocyte activities under shear flow in men. J Thromb Haemost 1:2031–2037. doi:10.1046/j.1538-7836.2003.00350.x
Wang JS, Li YS, Chen JC et al (2005) Effects of exercise training and deconditioning on platelet aggregation induced by alternating shear stress in men. Arterioscler Thromb Vasc Biol 25:454–460. doi:10.1161/01.ATV.0000151987.04607.24
Wang JS, Chang CY, Chow SE et al (2007) Exercise modulates platelet-nasopharyngeal carcinoma cell aggregation and subsequent tissue factor and matrix metalloproteinase activities. J Appl Physiol 103:763–770. doi:10.1152/japplphysiol.00165.2007
Westerlind KC (2003) Physical activity and cancer prevention-mechanisms. Med Sci Sports Exerc 35:1834–1840. doi:10.1249/01.MSS.0000093619.37805.B7
Yang EV, Sood AK, Chen M, Li Y, Eubank TD, Marsh CB, Jewell S, Flavahan NA, Morrison C, Yeh PE, Lemeshow S, Glaser R (2006) Norepinephrine up-regulates the expression of vascular endothelial growth factor, matrix metalloproteinase (MMP)-2, and MMP-9 in nasopharyngeal carcinoma tumor cells. Cancer Res 66:10357–10364. doi:10.1158/0008-5472.CAN-06-2496
Acknowledgments
The study was supported by the National Science Council of Taiwan (Grant 95-2314-B-182-035-MY3). The authors would like to thank the volunteers for their enthusiastic participation in this study.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Chen, YW., Chen, JK. & Wang, JS. Exercise affects platelet-promoted tumor cell adhesion and invasion to endothelium. Eur J Appl Physiol 105, 393–401 (2009). https://doi.org/10.1007/s00421-008-0916-2
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00421-008-0916-2