Skip to main content

Advertisement

SpringerLink
Log in

Platelets and extracellular vesicles in cancer: diagnostic and therapeutic implications

  • Published:
Cancer and Metastasis Reviews Aims and scope Submit manuscript

Abstract

Several pieces of evidence support the role of activated platelets in the development of the chronic inflammation-related diseases, such as atherothrombosis and cancer, mainly via the release of soluble factors and microparticles (MPs). Platelets and MPs contain a repertoire of proteins and genetic material (i.e., mRNAs and microRNAs) which may be influenced by the clinical condition of the individuals. In fact, platelets are capable of up-taking proteins and genetic material during their lifespan. Moreover, the content of platelet-derived MPs can be delivered to other cells, including stromal, immune, epithelial, and cancer cells, to change their phenotype and functions, thus contributing to cancer promotion and its metastasization. Platelets and MPs can play an indirect role in the metastatic process by helping malignant cells to escape from immunological surveillance. Furthermore, platelets and their derived MPs represent a potential source for blood biomarker development in oncology. This review provides an updated overview of the roles played by platelets and MPs in cancer and metastasis formation. The possible analysis of platelet and MP molecular signatures for the detection of cancer and monitoring of anticancer treatments is discussed. Finally, the potential use of MPs as vectors for drug delivery systems to cancer cells is put forward.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Flossmann, E., Rothwell, P. M., & for the British Doctors Aspirin Trial and the UK-TIA Aspirin Trial. (2007). Effect of aspirin on long-term risk of colorectal cancer: consistent evidence from randomised and observational studies. Lancet, 369(9573), 1603–1613.

    Article  PubMed  CAS  Google Scholar 

  2. Rothwell, P. M., Price, J. F., Fowkes, F. G., Zanchetti, A., Roncaglioni, M. C., Tognoni, G., Lee, R., Belch, J. F., Wilson, M., Mehta, Z., & Meade, T. W. (2011). Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials. Lancet, 377(9759), 31–41.

    Article  PubMed  CAS  Google Scholar 

  3. Rothwell, P. M., Wilson, M., Price, J. F., Belch, J. F., Meade, T. W., & Mehta, Z. (2012). Effect of daily aspirin on risk of cancer metastasis: a study of incident cancers during randomised controlled trials. Lancet, 379(9826), 1591–1601.

    Article  PubMed  CAS  Google Scholar 

  4. Rothwell, P. M., Price, J. F., Fowkes, F. G., Zanchetti, A., Roncaglioni, M. C., Tognoni, G., Lee, R., Belch, J. F., Wilson, M., Mehta, Z., & Meade, T. W. (2012). Short-term effects of daily aspirin on cancer incidence, mortality, and non-vascular death: analysis of the time course of risks and benefits in 51 randomised controlled trials. Lancet, 379(9826), 1602–1612.

    Article  PubMed  CAS  Google Scholar 

  5. Algra, A. M., & Rothwell, P. M. (2012). Effects of regular aspirin on long-term cancer incidence and metastasis: a systemic comparison of evidence from observational studies versus randomised trials. The Lancet Oncology, 13(5), 518–527.

    Article  PubMed  CAS  Google Scholar 

  6. Thun, M. J., Jacobs, E. J., & Patrono, C. (2012). The role of aspirin in cancer prevention. Nature Reviews. Clinical Oncology, 9(5), 259–267.

    Article  PubMed  CAS  Google Scholar 

  7. Dovizio, M., Bruno, A., Tacconelli, S., & Patrignani, P. (2013). Mode of action of aspirin as a chemopreventive agent. Recent Results in Cancer Research, 191, 39–65.

    Article  PubMed  CAS  Google Scholar 

  8. Patrono, C., Patrignani, P., & García Rodríguez, L. A. (2001). Cyclooxygenase-selective inhibition of prostanoid formation: transducing biochemical selectivity into clinical read-outs. The Journal of Clinical Investigation, 108(1), 7–13.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Patrignani, P., & Patrono, C. (2016). Aspirin and Cancer. Journal of the American College of Cardiology, 68(9), 967–976.

    Article  PubMed  CAS  Google Scholar 

  10. Best, M. G., Sol, N., Kooi, I., Tannous, J., Westerman, B. A., Rustenburg, F., Schellen, P., Verschueren, H., Post, E., Koster, J., Ylstra, B., Ameziane, N., Dorsman, J., Smit, E. F., Verheul, H. M., Noske, D. P., Reijneveld, J. C., Nilsson, R. J. A., Tannous, B. A., Wesseling, P., & Wurdinger, T. (2015). RNA-Seq of tumor-educated platelets enables blood-based pan-cancer, multiclass, and molecular pathway cancer diagnostics. Cancer Cell, 28(5), 666–676.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Best MG, Sol N, In 't Veld SGJG, Vancura A, Muller M, Niemeijer AN, et al. (2017) Swarm intelligence-enhanced detection of non-small-cell lung cancer using tumor-educated platelets. Cancer Cell. 32(2):238–52.

    Article  PubMed  CAS  Google Scholar 

  12. Best, M. G., Vancura, A., & Wurdinger, T. (2017). Platelet RNA as a circulating biomarker trove for cancer diagnostics. Journal of Thrombosis and Haemostasis, 15(7), 1295–1306.

    Article  PubMed  CAS  Google Scholar 

  13. Kune, G. A., Kune, S., & Watson, L. F. (1988). Colorectal cancer risk, chronic illnesses, operations, and medications: case control results from the Melbourne Colorectal Cancer Study. Cancer Research, 48(15), 4399–4404.

    PubMed  CAS  Google Scholar 

  14. Cole, B. F., Logan, R. F., Halabi, S., Benamouzig, R., Sandler, R. S., Grainge, M. J., Chaussade, S., & Baron, J. A. (2009). Aspirin for the chemoprevention of colorectal adenomas: meta-analysis of the randomized trials. Journal of the National Cancer Institute, 101(4), 256–266.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Burn, J., Bishop, D. T., Mecklin, J. P., Macrae, F., Möslein, G., Olschwang, S., Bisgaard, M. L., Ramesar, R., Eccles, D., Maher, E. R., Bertario, L., Jarvinen, H. J., Lindblom, A., Evans, D. G., Lubinski, J., Morrison, P. J., Ho, J. W., Vasen, H. F., Side, L., Thomas, H. J., Scott, R. J., Dunlop, M., Barker, G., Elliott, F., Jass, J. R., Fodde, R., Lynch, H. T., Mathers, J. C., & CAPP2 Investigators. (2008). Effect of aspirin or resistant starch on colorectal neoplasia in the Lynch syndrome. The New England Journal of Medicine, 359(24), 2567–2578.

    Article  PubMed  CAS  Google Scholar 

  16. Burn, J., Gerdes, A. M., Macrae, F., Mecklin, J. P., Moeslein, G., Olschwang, S., Eccles, D., Evans, D. G., Maher, E. R., Bertario, L., Bisgaard, M. L., Dunlop, M. G., Ho, J. W., Hodgson, S. V., Lindblom, A., Lubinski, J., Morrison, P. J., Murday, V., Ramesar, R., Side, L., Scott, R. J., Thomas, H. J., Vasen, H. F., Barker, G., Crawford, G., Elliott, F., Movahedi, M., Pylvanainen, K., Wijnen, J. T., Fodde, R., Lynch, H. T., Mathers, J. C., Bishop, D. T., & CAPP2 Investigators. (2011). Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial. Lancet, 378(9809), 2081–2087.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Patrono, C. (2015). The multifaceted clinical readouts of platelet inhibition by low-dose aspirin. Journal of the American College of Cardiology, 66(1), 74–85.

    Article  PubMed  CAS  Google Scholar 

  18. Simmons, D. L., Botting, R. M., & Hla, T. (2004). Cyclooxygenase isozymes: the biology of prostaglandin synthesis and inhibition. Pharmacological Reviews, 56(3), 387–437.

    Article  PubMed  CAS  Google Scholar 

  19. Loll, P. J., Picot, D., & Garavito, R. M. (1995). The structural basis of aspirin activity inferred from the crystal structure of inactivated prostaglandin H2 synthase. Nature Structural Biology, 2(8), 637–643.

    Article  PubMed  CAS  Google Scholar 

  20. Lecomte, M., Laneuville, O., Ji, C., DeWitt, D. L., & Smith, W. L. (1996). Acetylation of human prostaglandin endoperoxide synthase-2 (cyclooxygenase-2) by aspirin. The Journal of Biological Chemistry, 269(18), 13207–13215.

    Google Scholar 

  21. Patrignani, P., & Patrono, C. (2015). Cyclooxygenase inhibitors: from pharmacology to clinical read-outs. Biochimica et Biophysica Acta, 1851(4), 422–432.

    Article  PubMed  CAS  Google Scholar 

  22. Patrono, C., Baigent, C., Hirsh, J., & Roth, G. (2008). Antiplatelet drugs: American College of Chest Physicians evidence-based clinical practice guidelines (8th edition). Chest, 133(6 Suppl), 199S–233S.

    Article  PubMed  CAS  Google Scholar 

  23. Davì, G., & Patrono, C. (2007). Platelet activation and atherothrombosis. The New England Journal of Medicine, 357(24), 2482–2494.

    Article  PubMed  Google Scholar 

  24. Patrono, C., Coller, B., FitzGerald, G. A., Hirsh, J., & Roth, G. (2004). Platelet-active drugs: the relationships among dose, effectiveness, and side effects: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest, 126(Suppl 3), 234S–264S.

    Article  PubMed  CAS  Google Scholar 

  25. Bibbins-Domingo, K., & Preventive Services Task Force, U. S. (2016). Aspirin use for the primary prevention of cardiovascular disease and colorectal cancer: U.S. Preventive Services Task Force recommendation statement. Annals of Internal Medicine, 164(12), 836–845.

    Article  PubMed  Google Scholar 

  26. Dovizio, M., Sacco, A., & Patrignani, P. (2017). Curbing tumorigenesis and malignant progression through the pharmacological control of the wound healing process. Vascular Pharmacology, 89, 1–11.

    Article  PubMed  CAS  Google Scholar 

  27. Gawaz, M., Langer, H., & May, A. E. (2005). Platelets in inflammation and atherogenesis. The Journal of Clinical Investigation, 115(12), 3378–3384.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Contursi, A., Sacco, A., Grande, R., Dovizio, M., & Patrignani, P. (2017). Platelets as crucial partners for tumor metastasis: from mechanistic aspects to pharmacological targeting. Cellular and Molecular Life Sciences, 74(19), 3491–3507.

    Article  PubMed  Google Scholar 

  29. Wang, H., Fang, R., Wang, X. F., Zhang, F., Chen, D. Y., Zhou, B., Wang, H. S., Cai, S. H., & Du, J. (2013). Stabilization of Snail through AKT/GSK-3β signaling pathway is required for TNF-α-induced epithelial-mesenchymal transition in prostate cancer PC3 cells. European Journal of Pharmacology, 714(1–3), 48–55.

    Article  PubMed  CAS  Google Scholar 

  30. Kalluri, R., & Weinberg, R. A. (2009). The basics of epithelial-mesenchymal transition. The Journal of Clinical Investigation, 119(6), 1420–1428.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Mani, S. A., Guo, W., Liao, M. J., Eaton, E. N., Ayyanan, A., Zhou, A. Y., Brooks, M., Reinhard, F., Zhang, C. C., Shipitsin, M., Campbell, L. L., Polyak, K., Brisken, C., Yang, J., & Weinberg, R. A. (2008). The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell, 133(4), 704–715.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Labelle, M., Begum, S., & Hynes, R. O. (2011). Direct signaling between platelets and cancer cells induces an epithelial-mesenchymal-like transition and promotes metastasis. Cancer Cell, 20(5), 576–590.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Guillem-Llobat, P., Dovizio, M., Bruno, A., Ricciotti, E., Cufino, V., Sacco, A., Grande, R., Alberti, S., Arena, V., Cirillo, M., Patrono, C., FitzGerald, G., Steinhilber, D., Sgambato, A., & Patrignani, P. (2016). Aspirin prevents colorectal cancer metastasis in mice by splitting the crosstalk between platelets and tumor cells. Oncotarget, 7(22), 32462–32477.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Jing, Y., Han, Z., Zhang, S., Liu, Y., & Wei, L. (2011). Epithelial-mesenchymal transition in tumor microenvironment. Cell & Bioscience. https://doi.org/10.1186/2045-3701-1-29.

  35. Dovizio, M., Maier, T. J., Alberti, S., Di Francesco, L., Marcantoni, E., Münch, G., John, C. M., Suess, B., Sgambato, A., Steinhilber, D., & Patrignani, P. (2013). Pharmacological inhibition of platelet-tumor cell cross-talk prevents platelet-induced overexpression of cyclooxygenase-2 in HT29 human colon carcinoma cells. Molecular Pharmacology, 84(1), 25–40.

    Article  PubMed  CAS  Google Scholar 

  36. Dixon, D. A., Blanco, F. F., Bruno, A., & Patrignani, P. (2013). Mechanistic aspects of COX-2 expression in colorectal neoplasia. Recent Results in Cancer Research, 191, 7–37.

    Article  PubMed  CAS  Google Scholar 

  37. Zelenay, S., van der Veen, A. G., Böttcher, J. P., Snelgrove, K. J., Rogers, N., Acton, S. E., Chakravarty, P., Girotti, M. R., Marais, R., Quezada, S. A., Sahai, E., & Reis e Sousa, C. (2015). Cyclooxygenase-dependent tumor growth through evasion of immunity. Cell, 162(6), 1257–1270.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Arber, N., Eagle, C. J., Spicak, J., Rácz, I., Dite, P., Hajer, J., Zavoral, M., Lechuga, M. J., Gerletti, P., Tang, J., Rosenstein, R. B., Macdonald, K., Bhadra, P., Fowler, R., Wittes, J., Zauber, A. G., Solomon, S. D., Levin, B., & PreSAP Trial Investigators. (2006). Celecoxib for the prevention of colorectal adenomatous polyps. The New England Journal of Medicine, 355(9), 885–895.

    Article  PubMed  CAS  Google Scholar 

  39. Bertagnolli, M. M., Eagle, C. J., Zauber, A. G., Redston, M., Solomon, S. D., Kim, K., Tang, J., Rosenstein, R. B., Wittes, J., Corle, D., Hess, T. M., Woloj, G. M., Boisserie, F., Anderson, W. F., Viner, J. L., Bagheri, D., Burn, J., Chung, D. C., Dewar, T., Foley, T. R., Hoffman, N., Macrae, F., Pruitt, R. E., Saltzman, J. R., Salzberg, B., Sylwestrowicz, T., Gordon, G. B., Hawk, E. T., & APC Study Investigators. (2006). Celecoxib for the prevention of sporadic colorectal adenomas. The New England Journal of Medicine, 355(9), 873–884.

    Article  PubMed  CAS  Google Scholar 

  40. Baron, J. A., Sandler, R. S., Bresalier, R. S., Quan, H., Riddell, R., Lanas, A., Bolognese, J. A., Oxenius, B., Horgan, K., Loftus, S., Morton, D. G., & APPROVe Trial Investigators. (2006). A randomized trial of rofecoxib for the chemoprevention of colorectal adenomas. Gastroenterology, 131(6), 1674–1682.

    Article  PubMed  CAS  Google Scholar 

  41. Grosser, T., Fries, S., & FitzGerald, G. A. (2006). Biological basis for the cardiovascular consequences of COX-2 inhibition: therapeutic challenges and opportunities. The Journal of Clinical Investigation, 116, 4–15.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Li, H., Zhu, F., Boardman, L. A., Wang, L., Oi, N., Liu, K., Li, X., Fu, Y., Limburg, P. J., Bode, A. M., & Dong, Z. (2015). Aspirin prevents colorectal cancer by normalizing EGFR expression. EBioMedicine, 2(5), 447–455.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Tsujii, M., & DuBois, R. N. (1995). Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing prostaglandin endoperoxide synthase 2. Cell, 83(2), 493–501.

    Article  PubMed  CAS  Google Scholar 

  44. Jänne, P. A., & Mayer, R. J. (2000). Chemoprevention of colorectal cancer. The New England Journal of Medicine, 342(26), 1960–1968.

    Article  PubMed  Google Scholar 

  45. Patrono, C., & Rocca, B. (2008). Aspirin: promise and resistance in the new millennium. Arteriosclerosis, Thrombosis, and Vascular Biology, 28(3), s25–s32.

    Article  PubMed  CAS  Google Scholar 

  46. Dovizio, M., Tacconelli, S., Sostres, C., Ricciotti, E., & Patrignani, P. (2012). Mechanistic and pharmacological issues of aspirin as an anticancer agent. Pharmaceuticals (Basel, Switzerland), 5(12), 1346–1371.

    Article  CAS  Google Scholar 

  47. Gay, L. J., & Felding-Habermann, B. (2011). Contribution of platelets to tumour metastasis. Nature Reviews. Cancer, 11(2), 123–134.

    Article  PubMed  CAS  Google Scholar 

  48. Felding-Habermann, B., Habermann, R., Saldívar, E., & Ruggeri, Z. M. (1996). Role of beta3 integrins in melanoma cell adhesion to activated platelets under flow. The Journal of Biological Chemistry, 271(10), 5892–5900.

    Article  PubMed  CAS  Google Scholar 

  49. Lonsdorf, A. S., Krämer, B. F., Fahrleitner, M., Schönberger, T., Gnerlich, S., Ring, S., Gehring, S., Schneider, S. W., Kruhlak, M. J., Meuth, S. G., Nieswandt, B., Gawaz, M., Enk, A. H., & Langer, H. F. (2012). Engagement of αIIbβ3 (GPIIb/IIIa) with ανβ3 integrin mediates interaction of melanoma cells with platelets: a connection to hematogenous metastasis. The Journal of Biological Chemistry, 287(3), 2168–2178.

    Article  PubMed  CAS  Google Scholar 

  50. Mitrugno, A., Williams, D., Kerrigan, S. W., & Moran, N. (2014). A novel and essential role for FcγRIIa in cancer cell-induced platelet activation. Blood, 123(2), 249–260.

    Article  PubMed  CAS  Google Scholar 

  51. Mammadova-Bach, E., Zigrino, P., Brucker, C., Bourdon, C., Freund, M., De Arcangelis, A., Abrams, S. I., Orend, G., Gachet, C., & Mangin, P. H. (2016). Platelet integrin α6β1 controls lung metastasis through direct binding to cancer cell-derived ADAM9. JCI Insight, 1(14), e88245.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Mannori, G., Crottet, P., Cecconi, O., Hanasaki, K., Aruffo, A., Nelson, R. M., Varki, A., & Bevilacqua, M. P. (1995). Differential colon cancer cell adhesion to E-, P-, and L-selectin: role of mucin-type glycoproteins. Cancer Research, 55(19), 4425–4431.

    PubMed  CAS  Google Scholar 

  53. Gong, L., Cai, Y., Zhou, X., & Yang, H. (2012). Activated platelets interact with lung cancer cells through P-selectin glycoprotein ligand-1. Pathology Oncology Research, 18(4), 989–996.

    Article  PubMed  CAS  Google Scholar 

  54. Alves, C. S., Burdick, M. M., Thomas, S. N., Pawar, P., & Konstantopoulos, K. (2008). The dual role of CD44 as a functional P-selectin ligand and fibrin receptor in colon carcinoma cell adhesion. American Journal of Physiology. Cell Physiology, 294(4), C907–C916.

    Article  PubMed  CAS  Google Scholar 

  55. Larrucea, S., Butta, N., Rodriguez, R. B., Alonso-Martin, S., Arias-Salgado, E. G., Ayuso, M. S., & Parrilla, R. (2007). Podocalyxin enhances the adherence of cells to platelets. Cellular and Molecular Life Sciences, 64(22), 2965–2974.

    Article  PubMed  CAS  Google Scholar 

  56. Boukerche, H., Berthier-Vergnes, O., Tabone, E., Doré, J. F., Leung, L. L., & McGregor, J. L. (1989). Platelet-melanoma cell interaction is mediated by the glycoprotein IIb-IIIa complex. Blood, 74(2), 658–663.

    PubMed  CAS  Google Scholar 

  57. Suzuki-Inoue, K., Kato, Y., Inoue, O., Kaneko, M. K., Mishima, K., Yatomi, Y., Yamazaki, Y., Narimatsu, H., & Ozaki, Y. (2007). Involvement of the snake toxin receptor CLEC-2, in Podoplanin-mediated platelet activation, by cancer cells. The Journal of Biological Chemistry, 282(36), 25993–26001.

    Article  PubMed  CAS  Google Scholar 

  58. Chang, Y. W., Hsieh, P. W., Chang, Y. T., Lu, M. H., Huang, T. F., Chong, K. Y., Liao, H. R., Cheng, J. C., & Tseng, C. P. (2015). Identification of a novel platelet antagonist that binds to CLEC-2 and suppresses podoplanin-induced platelet aggregation and cancer metastasis. Oncotarget, 6(40), 42733–42748.

    PubMed  PubMed Central  Google Scholar 

  59. Ungerer, M., Rosport, K., Bültmann, A., Piechatzek, R., Uhland, K., Schlieper, P., Gawaz, M., & Münch, G. (2011). Novel antiplatelet drug revacept (dimeric glycoprotein VI-Fc) specifically and efficiently inhibited collagen-induced platelet aggregation without affecting general hemostasis in humans. Circulation, 123(17), 1891–1899.

    Article  PubMed  CAS  Google Scholar 

  60. Yang, R. Y., Rabinovich, G. A., & Liu, F. T. (2008). Galectins: structure, function and therapeutic potential. Expert Reviews in Molecular Medicine, 10, e17. https://doi.org/10.1017/S1462399408000719.

    Article  PubMed  Google Scholar 

  61. Yang, W. H., Lan, H. Y., Huang, C. H., Tai, S. K., Tzeng, C. H., Kao, S. Y., Wu, K. J., Hung, M. C., & Yang, M. H. (2012). RAC1 activation mediates Twist1-induced cancer cell migration. Nature Cell Biology, 14(4), 366–374.

    Article  PubMed  CAS  Google Scholar 

  62. Tímár, J., Tóvári, J., Rásó, E., Mészáros, L., Bereczky, B., & Lapis, K. (2005). Platelet-mimicry of cancer cells: epiphenomenon with clinical significance. Oncology, 69(3), 185–201.

    Article  PubMed  Google Scholar 

  63. Qiao, L., Liang, N., Zhang, J., Xie, J., Liu, F., Xu, D., Yu, X., & Tian, Y. (2015). Advanced research on vasculogenic mimicry in cancer. Journal of Cellular and Molecular Medicine, 19(2), 315–326.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Dixon, D. A., Tolley, N. D., Bemis-Standoli, K., Martinez, M. L., Weyrich, A. S., Morrow, J. D., Prescott, S. M., & Zimmerman, G. A. (2006). Expression of COX-2 in platelet-monocyte interactions occurs via combinatorial regulation involving adhesion and cytokine signaling. The Journal of Clinical Investigation, 116(10), 2727–2738.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  65. Eligini, S., Barbieri, S. S., Arenaz, I., Tremoli, E., & Colli, S. (2007). Paracrine up-regulation of monocyte cyclooxygenase-2 by platelets: role of transforming growth factor-beta1. Cardiovascular Research, 74(2), 270–278.

    Article  PubMed  CAS  Google Scholar 

  66. Achyut, B. R., Bader, D. A., Robles, A. I., Wangsa, D., Harris, C. C., Ried, T., & Yang, L. (2013). Inflammation-mediated genetic and epigenetic alterations drive cancer development in the neighboring epithelium upon stromal abrogation of TGF-beta signaling. PLoS Genetics, 9, e1003251. https://doi.org/10.1371/journal.pgen.1003251.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  67. Zhu, Y., Zhu, M., & Lance, P. (2012). IL1β-mediated stromal COX-2 signaling mediates proliferation and invasiveness of colonic epithelial cancer cells. Experimental Cell Research, 318(19), 2520–2530.

    Article  PubMed  CAS  Google Scholar 

  68. Caughey, G. E., Cleland, L. G., Gamble, J. R., & James, M. J. (2001). Up-regulation of endothelial cyclooxygenase-2 and prostanoid synthesis by platelets. Role of thromboxane A2. The Journal of Biological Chemistry, 276, 37839–37845.

    PubMed  CAS  Google Scholar 

  69. Servais, L., Wéra, O., Dibato Epoh, J., Delierneux, C., Bouznad, N., Rahmouni, S., Mazzucchelli, G., Baiwir, D., Delvenne, P., Lancellotti, P., & Oury, C. (2018). Platelets contribute to the initiation of colitis-associated cancer by promoting immunosuppression. Journal of Thrombosis and Haemostasis, 16(4), 762–777.

    Article  PubMed  CAS  Google Scholar 

  70. Kitamura, T., Qian, B. Z., & Pollard, J. W. (2015). Immune cell promotion of metastasis. Nature Reviews. Immunology, 15(2), 73–86.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  71. Ali, R. A., Wuescher, L. M., & Worth, R. G. (2015). Platelets: essential components of the immune system. Current Trends in Immunology, 16, 65–78.

    PubMed  PubMed Central  Google Scholar 

  72. Hinterleitner, C., Strähle, J., Wirths, S., Bugl, S., Malenke, E., Mueller, M. R., Kanz, L., & Kopp, H.-G. (2017). Platelet programmed cell death ligand 1 (pPDL-1) is a prognostic marker in advanced lung cancer. Blood, 130, 3610.

    Google Scholar 

  73. Juneja, V. R., McGuire, K. A., Manguso, R. T., LaFleur, M. W., Collins, N., Haining, W. N., Freeman, G. J., & Sharpe, A. H. (2017). PD-L1 on tumor cells is sufficient for immune evasion in immunogenic tumors and inhibits CD8 T cell cytotoxicity. The Journal of Experimental Medicine, 214(4), 895–904.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  74. Dang, T. O., Ogunniyi, A., Barbee, M. S., & Drilon, A. (2016). Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer. Expert Review of Anticancer Therapy, 16(1), 13–20.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  75. Rachidi, S., Metelli, A., Riesenberg, B., Wu, B. X., Nelson, M. H., Wallace, C., Paulos, C. M., Rubinstein, M. P., Garrett-Mayer, E., Hennig, M., Bearden, D. W., Yang, Y., Liu, B., & Li, Z. (2017). Platelets subvert T cell immunity against cancer via GARP-TGFβ axis. Science Immunology, 2(11), eaai7911. https://doi.org/10.1126/sciimmunol.aai7911.

    Article  PubMed  PubMed Central  Google Scholar 

  76. Sitia, G., Aiolfi, R., Di Lucia, P., Mainetti, M., Fiocchi, A., Mingozzi, F., Esposito, A., Ruggeri, Z. M., Chisari, F. V., Iannacone, M., & Guidotti, L. G. (2012). Antiplatelet therapy prevents hepatocellular carcinoma and improves survival in a mouse model of chronic hepatitis B. Proceedings of the National Academy of Sciences of the United States of America, 109(32), E2165–E2172.

    Article  PubMed  PubMed Central  Google Scholar 

  77. Guidotti, L. G., & Chisari, F. V. (2006). Immunobiology and pathogenesis of viral hepatitis. Annual Review of Pathology, 1, 23–61.

    Article  PubMed  CAS  Google Scholar 

  78. Elzey, B. D., Tian, J., Jensen, R. J., Swanson, A. K., Lees, J. R., Lentz, S. R., Stein, C. S., Nieswandt, B., Wang, Y., Davidson, B. L., & Ratliff, T. L. (2003). Platelet-mediated modulation of adaptive immunity. A communication link between innate and adaptive immune compartments. Immunity, 19(1), 9–19.

    Article  PubMed  CAS  Google Scholar 

  79. Henn, V., Slupsky, J. R., Gräfe, M., Anagnostopoulos, I., Förster, R., Müller-Berghaus, G., & Kroczek, R. A. (1998). CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells. Nature, 391(6667), 591–594.

    Article  PubMed  CAS  Google Scholar 

  80. Tripodi, A., & Mannucci, P. M. (2011). The coagulopathy of chronic liver disease. The New England Journal of Medicine, 365(2), 147–156.

    Article  PubMed  CAS  Google Scholar 

  81. Cloutier, N., Allaeys, I., Marcoux, G., Machlus, K. R., Mailhot, B., Zufferey, A., Levesque, T., Becker, Y., Tessandier, N., Melki, I., Zhi, H., Poirier, G., Rondina, M. T., Italiano, J. E., Flamand, L., McKenzie, S. E., Cote, F., Nieswandt, B., Khan, W. I., Flick, M. J., Newman, P. J., Lacroix, S., Fortin, P. R., & Boilard, E. (2018). Platelets release pathogenic serotonin and return to circulation after immune complex-mediated sequestration. Proceedings of the National Academy of Sciences of the United States of America, 115(7), E1550–E1559.

    Article  PubMed  PubMed Central  Google Scholar 

  82. Cohen, J. D., Li, L., Wang, Y., Thoburn, C., Afsari, B., Danilova, L., Douville, C., Javed, A. A., Wong, F., Mattox, A., Hruban, R. H., Wolfgang, C. L., Goggins, M. G., Dal Molin, M., Wang, T. L., Roden, R., Klein, A. P., Ptak, J., Dobbyn, L., Schaefer, J., Silliman, N., Popoli, M., Vogelstein, J. T., Browne, J. D., Schoen, R. E., Brand, R. E., Tie, J., Gibbs, P., Wong, H. L., Mansfield, A. S., Jen, J., Hanash, S. M., Falconi, M., Allen, P. J., Zhou, S., Bettegowda, C., Diaz Jr., L. A., Tomasetti, C., Kinzler, K. W., Vogelstein, B., Lennon, A. M., & Papadopoulos, N. (2018). Detection and localization of surgically resectable cancers with a multi-analyte blood test. Science, 359(6378), 926–930.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  83. Nilsson, R. J., Balaj, L., Hulleman, E., van Rijn, S., Pegtel, D. M., Walraven, M., Widmark, A., Gerritsen, W. R., Verheul, H. M., Vandertop, W. P., Noske, D. P., Skog, J., & Würdinger, T. (2011). Blood platelets contain tumor-derived RNA biomarkers. Blood, 118(13), 3680–3683.

    Article  PubMed  Google Scholar 

  84. Burnouf, T., Goubran, H. A., Chou, M. L., Devos, D., & Radosevic, M. (2014). Platelet microparticles: detection and assessment of their paradoxical functional roles in disease and regenerative medicine. Blood Reviews, 28(4), 155–166.

    Article  PubMed  CAS  Google Scholar 

  85. Janowska-Wieczorek, A., Wysoczynski, M., Kijowski, J., Marquez-Curtis, L., Machalinski, B., Ratajczak, J., & Ratajczak, M. Z. (2005). Microvesicles derived from activated platelets induce metastasis and angiogenesis in lung cancer. International Journal of Cancer, 113(5), 752–760.

    Article  PubMed  CAS  Google Scholar 

  86. Italiano Jr., J. E., Mairuhu, A. T., & Flaumenhaft, R. (2010). Clinical relevance of microparticles from platelets and megakaryocytes. Current Opinion in Hematology, 17(6), 578–584.

    Article  PubMed  PubMed Central  Google Scholar 

  87. Ratajczak, J., Wysoczynski, M., Hayek, F., Janowska-Wieczorek, A., & Ratajczak, M. Z. (2006). Membrane-derived microvesicles: important and underappreciated mediators of cell-to-cell communication. Leukemia, 20(9), 1487–1495.

    Article  PubMed  CAS  Google Scholar 

  88. Baj-Krzyworzeka, M., Majka, M., Pratico, D., Ratajczak, J., Vilaire, G., Kijowski, J., Reca, R., Janowska-Wieczorek, A., & Ratajczak, M. Z. (2002). Platelet-derived microparticles stimulate proliferation, survival, adhesion, and chemotaxis of hematopoietic cells. Experimental Hematology, 30(5), 450–459.

    Article  PubMed  CAS  Google Scholar 

  89. Barry, O. P., Kazanietz, M. G., Praticò, D., & FitzGerald, G. A. (1999). Arachidonic acid in platelet microparticles up-regulates cyclooxygenase-2-dependent prostaglandin formation via a protein kinase C/mitogen-activated protein kinase-dependent pathway. The Journal of Biological Chemistry, 274(11), 7545–7556.

    Article  PubMed  CAS  Google Scholar 

  90. Barry, O. P., Pratico, D., Lawson, J. A., & FitzGerald, G. A. (1997). Transcellular activation of platelets and endothelial cells by bioactive lipids in platelet microparticles. The Journal of Clinical Investigation, 99(9), 2118–2127.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  91. Risitano, A., Beaulieu, L. M., Vitseva, O., & Freedman, J. E. (2012). Platelets and platelet-like particles mediate intercellular RNA transfer. Blood, 119(26), 6288–6295.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  92. Diehl, P., Fricke, A., Sander, L., Stamm, J., Bassler, N., Htun, N., Ziemann, M., Helbing, T., El-Osta, A., Jowett, J. B., & Peter, K. (2012). Microparticles: major transport vehicles for distinct microRNAs in circulation. Cardiovascular Research, 93(4), 633–644.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  93. Laffont, B., Corduan, A., Plé, H., Duchez, A. C., Cloutier, N., Boilard, E., & Provost, P. (2013). Activated platelets can deliver mRNA regulatory Ago2•microRNA complexes to endothelial cells via microparticles. Blood, 122(2), 253–261.

    Article  PubMed  CAS  Google Scholar 

  94. Tang, M., Jiang, L., Lin, Y., Wu, X., Wang, K., He, Q., Wang, X., & Li, W. (2017). Platelet microparticle-mediated transfer of miR-939 to epithelial ovarian cancer cells promotes epithelial to mesenchymal transition. Oncotarget, 8(57), 97464–97475.

    Article  PubMed  PubMed Central  Google Scholar 

  95. Michael, J. V., Wurtzel, J. G. T., Mao, G. F., Rao, A. K., Kolpakov, A., Sabri, A., Hoffman, N. E., Rajan, S., Tomar, D., Madesh, M., Nieman, M. T., Yu, J., Edelstein, L. C., Rowley, J. W., Weyrich, A. S., & Goldfinger, L. E. (2017). Platelet microparticles infiltrating solid tumors transfer miRNAs that suppress tumor growth. Blood, 130(5), 567–580.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  96. Linke, B., Schreiber, Y., Picard-Willems, B., Slattery, P., Nüsing, R. M., Harder, S., Geisslinger, G., & Scholich, K. (2017). Activated platelets induce an anti-inflammatory response of monocytes/macrophages through cross-regulation of PGE(2) and cytokines. Mediators of Inflammation, 2017, 1–14. https://doi.org/10.1155/2017/1463216.

    Article  CAS  Google Scholar 

  97. Boilard, E. N., Larabee, P. A., Watts, K., et al. (2010). Platelets amplify inflammation in arthritis via collagen-dependent microparticle production. Science, 29(5965), 580–583.

    Article  CAS  Google Scholar 

  98. Vasina, E. M., Cauwenberghs, S., Feijge, M. A., Heemskerk, J. W., Weber, C., & Koenen, R. R. (2011). Microparticles from apoptotic platelets promote resident macrophage differentiation. Cell Death & Disease, 2, e211. https://doi.org/10.1038/cddis.2011.94.

    Article  CAS  Google Scholar 

  99. Sadallah, S., Eken, C., Martin, P. J., & Schifferli, J. A. (2011). Microparticles (ectosomes) shed by stored human platelets downregulate macrophages and modify the development of dendritic cells. Journal of Immunology, 186(11), 6543–6552.

    Article  CAS  Google Scholar 

  100. Laffont, B., Rousseau, M., Duchez, A. C., Lee, C. H., Boilard, E., & Provost, P. (2016). Platelet microparticles reprogram macrophage gene expression and function. Thrombosis and Haemostasis, 115(2), 311–323.

    Article  PubMed  Google Scholar 

  101. Soga, F., Katoh, N., Inoue, T., & Kishimoto, S. (2007). Serotonin activates human monocytes and prevents apoptosis. The Journal of Investigative Dermatology, 127(8), 1947–1955.

    Article  PubMed  CAS  Google Scholar 

  102. Duchez, A. C., Boudreau, L. H., Naika, G. S., Bollinger, J., Belleannée, C., Cloutier, N., Laffont, B., Mendoza-Villarroel, R. E., Lévesque, T., Rollet-Labelle, E., Rousseau, M., Allaeys, I., Tremblay, J. J., Poubelle, P. E., Lambeau, G., Pouliot, M., Provost, P., Soulet, D., Gelb, M. H., & Boilard, E. (2015). Platelet microparticles are internalized in neutrophils via the concerted activity of 12-lipoxygenase and secreted phospholipase A2-IIA. Proceedings of the National Academy of Sciences of the United States of America, 112, E3564–E3573. https://doi.org/10.1073/pnas.1507905112.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  103. Sprague, D. L., Elzey, B. D., Crist, S. A., Waldschmidt, T. J., Jensen, R. J., & Ratliff, T. L. (2008). Platelet-mediated modulation of adaptive immunity: unique delivery of CD154 signal by platelet-derived membrane vesicles. Blood, 111(10), 5028–5036.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  104. Kim, H. K., Song, K. S., Park, Y. S., Kang, Y. H., Lee, Y. J., Lee, K. R., Kim, H. K., Ryu, K. W., Bae, J. M., & Kim, S. (2003). Elevated levels of circulating platelet microparticles, VEGF, IL-6 and RANTES in patients with gastric cancer: possible role of a metastasis predictor. European Journal of Cancer, 39(2), 184–191.

    Article  PubMed  CAS  Google Scholar 

  105. Mege, D., Panicot-Dubois, L., Ouaissi, M., Robert, S., Sielezneff, I., Sastre, B., Dignat-George, F., & Dubois, C. (2016). The origin and concentration of circulating microparticles differ according to cancer type and evolution: a prospective single-center study. International Journal of Cancer, 138(4), 939–948.

    Article  PubMed  CAS  Google Scholar 

  106. Wang, C. C., Tseng, C. C., Chang, H. C., Huang, K. T., Fang, W. F., Chen, Y. M., Yang, C. T., Hsiao, C. C., Lin, M. C., Ho, C. K., & Yip, H. K. (2017). Circulating microparticles are prognostic biomarkers in advanced non-small cell lung cancer patients. Oncotarget, 8(44), 75952–75967.

    PubMed  PubMed Central  Google Scholar 

  107. Fais, S., O’Driscoll, L., Borras, F. E., Buzas, E., Camussi, G., Cappello, F., Carvalho, J., Cordeiro da Silva, A., Del Portillo, H., El Andaloussi, S., Ficko Trček, T., Furlan, R., Hendrix, A., Gursel, I., Kralj-Iglic, V., Kaeffer, B., Kosanovic, M., Lekka, M. E., Lipps, G., Logozzi, M., Marcilla, A., Sammar, M., Llorente, A., Nazarenko, I., Oliveira, C., Pocsfalvi, G., Rajendran, L., Raposo, G., Rohdem, E., Siljander, P., van Niel, G., Vasconcelos, M. H., Yáñez-Mó, M., Yliperttula, M. L., Zarovni, N., Zavec, A. B., & Giebel, B. (2016). Evidencebased clinical use of nanoscale extracellular vesicles in nanomedicine. ACS Nano, 10(4), 3886–3899.

    Article  PubMed  CAS  Google Scholar 

  108. Escudier, B., Dorval, T., Chaput, N., André, F., Caby, M. P., Novault, S., Flament, C., Leboulaire, C., Borg, C., Amigorena, S., Boccaccio, C., Bonnerot, C., Ohellin, O., Movassagh, M., Piperno, S., Robert, C., Serra, V., Valente, N., Le Pecq, J. B., Spatz, A., Lantz, O., Tursz, T., Angevin, E., & Zitvogel, L. (2005). Vaccination of metastatic melanoma patients with autologous dendritic cell (DC) derived-exosomes: results of the first phase I clinical trial. Journal of Translational Medicine, 3(1), 10.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  109. Kim, S. M., & Kim, H. S. (2017). Engineering of extracellular vesicles as drug delivery vehicles. Stem Cell Investig. https://doi.org/10.21037/sci.2017.08.07.

Download references

Author information

Author notes

  1. Melania Dovizio and Annalisa Bruno contributed equally to this work.

Authors and Affiliations

  1. Department of Neuroscience, Imaging and Clinical Sciences and Center for Research on Aging and Translational Medicine (CeSI-MeT), Systems Pharmacology Laboratory, “G. d’Annunzio” University, Chieti, Italy

    Melania Dovizio, Annalisa Bruno, Annalisa Contursi, Rosalia Grande & Paola Patrignani

Authors
  1. Melania Dovizio
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Annalisa Bruno
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Annalisa Contursi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rosalia Grande
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Paola Patrignani
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Paola Patrignani.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dovizio, M., Bruno, A., Contursi, A. et al. Platelets and extracellular vesicles in cancer: diagnostic and therapeutic implications. Cancer Metastasis Rev 37, 455–467 (2018). https://doi.org/10.1007/s10555-018-9730-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10555-018-9730-4

Keywords

Search

Navigation