Obstetrics, Gynecology and Reproduction

Advanced search

Platelets, thrombo-inflammation and cancer

Full Text:


It has long been recognized a crucial role played by platelets in thrombosis and hemostasis. Along with that, laboratory and clinical data suggest that platelets contribute to tumor progression and metastasis through a variety of interactions with cancer cells. During oncological process, the platelet function becomes modulated via their activation and increased aggregation being one of the risk factors for developing thrombosis in cancer patients. The platelets per se enhance tumor cell dissemination, activate endothelial cells, and attract immune cells to the primary and metastatic tumor sites. In this review, we summarize the current knowledge about the complex interactions between platelets and tumor cells, as well as cells of the microenvironment, and discuss the development of new antitumor agents aimed at various arms in platelet functioning.

About the Authors

E. V. Slukhanchuk
Sechenov University; Petrovsky National Research Centre of Surgery
Russian Federation

Ekaterina V. Slukhanchuk – MD, PhD, Associate Professor, Department of Obstetrics and Gynecology, Filatov Clinical Institute of Children’s Health; Obstetrician-Gynecologist, Department of Abdominal Surgery and Oncology 2

2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow, 119991
2 Abrikosovskiy Lane, Moscow, 119991

V. O. Bitsadze
Sechenov University
Russian Federation

Victoria O. Bitsadze – MD, Dr Sci Med, Professor of RAS, Professor, Department of Obstetrics and Gynecology, Filatov Clinical Institute of Children’s Health. Scopus Author ID: 6506003478. Researcher ID: F-8409-2017

2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow, 119991

J. Kh. Khizroeva
Sechenov University
Russian Federation

Jamilya Kh. Khizroeva – MD, Dr Sci Med, Professor, Department of Obstetrics and Gynecology, Filatov Clinical Institute of Children’s Health. Scopus Author ID: 57194547147. Researcher ID: F-8384-2017

2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow, 119991

M. V. Tretyakova
Sechenov University
Russian Federation

Maria V. Tretyakova – MD, PhD, Obstetrician-Gynecologist, Assistant, Department of Obstetrics and Gynecology, Filatov Clinical Institute of Children’s Health

2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow, 119991

A. G. Solopova
Sechenov University
Russian Federation

Antonina G. Solopova – MD, Dr Sci Med, Professor, Department of Obstetrics and Gynecology, Filatov Clinical Institute of Children's Health. Scopus Author ID: 6505479504. Researcher ID: Q-1385-2015

2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow, 119991

V. N. Galkin
City Clinical Oncological Hospital № 1, Moscow City Healthcare Department
Russian Federation

Vsevolod N. Galkin – MD, Dr Sci Med, Professor, Chief Physician 

17/1 Baumanskaya Str., Moscow, 105005

A. S. Shkoda
Vorokhobov City Clinical Hospital № 67, Moscow City Healthcare Department
Russian Federation

Andrey S. Shkoda – MD, Dr Sci Med, Professor, Chief Physician 

2/44 Salyama Adilya Str., Moscow, 123423

V. I. Tsibizova
Almazov National Medical Research Centre, Health Ministry of Russian Federation
Russian Federation

Valentina I. Tsibizova – MD, PhD, Obstetrician-Gynecologist, Research Laboratory of Operative Gynecology, Institute of Perinatology and Pediatrics; Physician, Department of Functional and Ultrasound Diagnostics 

2 Akkuratova Str., Saint Petersburg, 197341

V. I. Linnikov
Saint Paul German Medical and Diagnostic Center

Valery I. Linnikov – MD, PhD, Professor 

68/2 Novoselskogo Str., Odessa, 65023

Ismail Elalamy
Sechenov University; Medicine Sorbonne University; Hospital Tenon
Russian Federation

Ismail Elalamy – MD, Dr Sci Med, Professor, Department of Obstetrics and Gynecology, Filatov Clinical Institute of Children’s Health; Professor; Director of Hematology, Department of Thrombosis Center. Scopus Author ID: 7003652413. Researcher ID: AAC-9695-2019

2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow, 119991
12 Rue de l’École de Médecine, Paris, 75006, France
4 Rue de la Chine, Paris, 75020, France

J.-С. Gris
Sechenov University; University of Montpellier
Russian Federation

Jean-Christophe Gris – MD, Dr Sci Med, Professor, Department of Obstetrics and Gynecology, Filatov Clinical Institute of Children’s Health; Professor of Haematology, Head of the Laboratory of Haematology, Faculty of Biological and Pharmaceutical Sciences, Montpellier University and University Hospital of Nîmes. Scopus Author ID: 7005114260. Researcher ID: AAA-2923-2019

2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow, 119991
163 Rue Auguste Broussonnet, Montpellier, 34090, France

B. Brenner
Rambam Academic Hospital

Benjamin Brenner – MD, Dr Sci Med, Professor, Director of the Hematology and Bone Marrow Transplantation Institute; Director of the Department of Internal Medicine

8 Aliya-ha-Shniya Str., Haifa 31096

A. D. Makatsariya
Sechenov University
Russian Federation

Alexander D. Makatsariya – MD, Dr Sci Med, Academician of RAS, Professor, Head of the Department of Obstetrics and Gynecology, Filatov Clinical Institute of Children’s Health. Scopus Author ID: 57222220144. Researcher ID: M-5660-2016

2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow, 119991


1. Varki A. Trousseau's syndrome: multiple definitions and multiple mechanisms. Blood. 2007;110(6):1723–9.

2. Blom J.W., Doggen C.J., Osanto S., Rosendaal F.R. Malignancies, prothrombotic mutations, and the risk of venous thrombosis. JAMA. 2005;293(6):715–22.

3. Duan Q., Zhang H., Zheng J., Zhang L. Turning cold into hot: firing up the tumor microenvironment. Trends Cancer. 2020;6(7):605–18.

4. Mammadova-Bach E., Nagy M., Heemskerk J.W. et al. Store-operated calcium entry in thrombosis and thrombo-inflammation. Cell Calcium. 2019;77:39–48.

5. Scharf R.E. Platelet signaling in primary haemostasis and arterial thrombus formation: Part 1. Hamostaseologie. 2018;38(4):203–10.

6. Silverstein M.D., Heit J.A., Mohr D.N. et al. Trends in the incidence of deep vein thrombosis and pulmonary embolism: a 25-year population-based study. Arch Intern Med. 1998;158(6):585–93.

7. Abdel-Razeq H., Mansour A., Saadeh S.S. et al. The application of current proposed venous thromboembolism risk assessment model for ambulatory patients with cancer. Clin Appl Thromb Hemost. 2018;24(3):429–33.

8. Patell R., Rybicki L., McCrae K.R., Khorana A.A. Predicting risk of venous thromboembolism in hospitalized cancer patients: utility of a risk assessment tool. Am J Hematol. 2017;92(6):501–7.

9. Cravioto-Villanueva A., Luna-Perez P., Gutierrez-de la Barrera M. et al. Thrombocytosis as a predictor of distant recurrence in patients with rectal cancer. Arch Med Res. 2012;43(4):305–11.

10. Stone R.L., Nick A.M., McNeish I.A. et al. Paraneoplastic thrombocytosis in ovarian cancer. N Engl J Med. 2012;366(7):610–8.

11. Kaser A., Brandacher G., Steurer W. et al. Interleukin-6 stimulates thrombopoiesis through thrombopoietin: role in inflammatory thrombocytosis Blood. 2001;98(9):2720–5.

12. Besbes S., Shah S., Al-Dybiat I. et al. Thrombopoietin secretion by human ovarian cancer cells. Int J Cell Biol. 2017;2017:1873834.

13. Riedl J., Hell L., Kaider A. et al. Association of platelet activation markers with cancer-associated venous thromboembolism. Platelets. 2016;27(1):80–5.

14. Reddel C.J., Tan C.W., Chen V.M. Thrombin generation and cancer: contributors and consequences. Cancers (Basel). 2019;11(1):100.

15. Heinmöller E., Weinel R.J., Heidtmann H.H. et al. Studies on tumor-cellinduced platelet aggregation in human lung cancer cell lines. J Cancer Res Clin Oncol. 1996;122(12):735–44.

16. Heinmöller E., Schropp T., Kisker O. et al. Tumor cell-induced platelet aggregation in vitro by human pancreatic cancer cell lines. Scand J Gastroenterol. 1995;30(10):1008–16.

17. Gasic G.J., Gasic T.B., Stewart C.C. Antimetastatic effects associated with platelet reduction. Proc Natl Acad Sci U S A. 1968;61(1):46–52.

18. Lee H.-Y., Yu N.-Y., Lee S.-H. et al. Podoplanin promotes cancerassociated thrombosis and contributes to the unfavorable overall survival in an ectopic xenograft mouse model of oral cancer. Biomed J. 2020;43(2):146–62.

19. Lowe K.L., Navarro-Nunez L., Watson S.P. Platelet CLEC-2 and podoplanin in cancer metastasis. Thromb Res. 2012;129 Suppl 1:S30–7.

20. Suzuki-Inoue K. Platelets and cancer-associated thrombosis: focusing on the platelet activation receptor CLEC-2 and podoplanin. Blood. 2019;134(22):1912–8.

21. Zara M., Canobbio I., Visconte C. et al. Molecular mechanisms of platelet activation and aggregation induced by breast cancer cells. Cell Signal. 2018;48:45–53. https://doi.org10.1016/j.cellsig.2018.04.008.

22. Aghourian M.N., Lemarie C.A., Bertin F.-R., Blostein M.D. Prostaglandin E synthase is upregulated by Gas6 during cancer-induced venous thrombosis. Blood. 2016;127(6):769–77.

23. Meikle C.K., Meisler A.J., Bird C.M. et al. Platelet-T cell aggregates in lung cancer patients: Implications for thrombosis. PloS One. 2020;15(8):e0236966.

24. Rudzinski J.K., Govindasamy N.P., Lewis J.D., Jurasz P. The role of the androgen receptor in prostate cancer-induced platelet aggregation and platelet-induced invasion. J Thromb Haemost. 2020;18(11):2976–86.

25. Mitrugno A., Williams D., Kerrigan S.W., Moran N. A novel and essential role for FcγRIIa in cancer cell–induced platelet activation. Blood. 2014;123(2):249–60.

26. Hisada Y, Mackman N. Update from the laboratory: mechanistic studies of pathways of cancer-associated venous thrombosis using mouse models. Hematology Am Soc Hematol Educ Program. 2019;2019(1):182–6.

27. Shi C., Yang L., Braun A., Anders H.-J. Extracellular DNA – a danger signal triggering immunothrombosis. Front Immunol. 2020;11:568513.

28. Wen F., Shen A., Choi A. et al. Extracellular DNA in pancreatic cancer promotes cell invasion and metastasis. Cancer Res. 2013;73(14):4256–66.

29. Eelen G., Treps L., Li X., Carmeliet P. Basic and therapeutic aspects of angiogenesis updated. Circ Res. 2020;127(2):310–29.

30. Goubran H.A., Burnouf T., Radosevic M., El-Ekiaby M. The platelet–cancer loop. Eur J Inter Med. 2013;24(5):393–400.

31. Zaslavsky A., Baek K.-H., Lynch R.C. et al. Platelet-derived thrombospondin-1 is a critical negative regulator and potential biomarker of angiogenesis. Blood. 2010;115(22):4605–13.

32. Battinelli E.M., Markens B.A., Italiano J.E. Release of angiogenesis regulatory proteins from platelet alpha granules: modulation of physiologic and pathologic angiogenesis. Blood. 2011;118(5):1359–69.

33. Salgado R., Junius S., Benoy I. et al. Circulating interleukin-6 predicts survival in patients with metastatic breast cancer. Int J Cancer. 2003;103(5):642–6.

34. Feng W., Madajka M., Kerr B.A. et al. A novel role for platelet secretion in angiogenesis: mediating bone marrow–derived cell mobilization and homing. Blood. 2011;117(14):3892–902.

35. Kuznetsov H.S., Marsh T., Markens B.A. et al. Identification of luminal breast cancers that establish a tumor-supportive macroenvironment defined by proangiogenic platelets and bone marrow–derived cells. Cancer Discov. 2012;2(12):1150–65.

36. Neufeld G., Cohen T., Gengrinovitch S., Poltorak Z. Vascular endothelial growth factor (VEGF) and its receptors. FASEB J. 1999;13(1):9–22.

37. Wojtukiewicz M.Z., Sierko E., Hempel D. et al. Platelets and cancer angiogenesis nexus. Cancer Metastasis Rev. 2017;36(2):249–62.

38. Borgström P., Discipio R., Maione T. Recombinant platelet factor 4, an angiogenic marker for human breast carcinoma. Anticancer Res. 1998;18(6A):4035–41.

39. Varner J.A., Nakada M.T., Jordan R.E., Coller B.S. Inhibition of angiogenesis and tumor growth by murine 7E3, the parent antibodyof c7E3 Fab (abciximab; ReoProTM). Angiogenesis. 1999;3(1):53–60.

40. Huang Z., Miao X., Patarroyo M. et al. Tetraspanin CD 151 and integrin α6β1 mediate platelet-enhanced endothelial colony forming cell angiogenesis. J Thromb Haemost. 2016;14(3):606–18.

41. Anene C., Graham A.M., Boyne J., Roberts W. Platelet microparticle delivered microRNA-Let-7a promotes the angiogenic switch. Biochim Biophys Acta Mol Basis Dis. 2018;1864(8):2633–43.

42. Bertozzi C.C., Schmaier A.A., Mericko P. et al. Platelets regulate lymphatic vascular development through CLEC-2–SLP-76 signaling. Blood. 2010;116(4):661–70.

43. Haining E.J., Lowe K.L., Wichaiyo S. et al. Lymphatic blood filling in CLEC2-deficient mouse models. Platelets. 2021;32(3):352–67.

44. Martini C., Thompson E.J., Hyslop S.R. et al. Platelets disrupt vasculogenic mimicry by cancer cells. Scientific Reports. 2020;10(1):1–18.

45. Ho-Tin-Noé B., Goerge T., Cifuni S.M. et al. Platelet granule secretion continuously prevents intratumor hemorrhage. Cancer Res. 2008;68(16):6851–8.

46. Demers M., Ho-Tin-Noé B., Schatzberg D. et al. Increased efficacy of breast cancer chemotherapy in thrombocytopenic mice. Cancer Res. 2011;71(5):1540–9.

47. Volz J., Mammadova-Bach E., Gil-Pulido J. et al. Inhibition of platelet GPVI induces intratumor hemorrhage and increases efficacy of chemotherapy in mice. Blood. 2019;133(25):2696–706.

48. Camerer E., Qazi A.A., Duong D.N. et al. Platelets, protease-activated receptors, and fibrinogen in hematogenous metastasis. Blood. 2004;104(2):397–401.

49. Palumbo J.S., Talmage K.E., Massari J.V. et al. Platelets and fibrin (ogen) increase metastatic potential by impeding natural killer cell–mediated elimination of tumor cells. Blood. 2005;105(1):178–85.

50. Coupland L.A., Chong B.H., Parish C.R. Platelets and P-selectin control tumor cell metastasis in an organ-specific manner and independently of NK cells. Cancer Res. 2012;72(18):4662–71.

51. Placke T., Örgel M., Schaller M. et al. Platelet-derived MHC class I confers a pseudonormal phenotype to cancer cells that subverts the antitumor reactivity of natural killer immune cells. Cancer Res. 2012;72(2):440–8.

52. Maurer S., Kropp K.N., Klein G. et al. Platelet-mediated shedding of NKG2D ligands impairs NK cell immune-surveillance of tumor cells. Oncoimmunology. 2017;7(2):e1364827.

53. Kopp H.-G., Placke T., Salih H.R. Platelet-derived transforming growth factor-beta down-regulates NKG2D thereby inhibiting natural killer cell antitumor reactivity. Cancer Res. 2009;69(19):7775–83.

54. Rachidi S., Metelli A., Riesenberg B. et al. Platelets subvert T cell immunity against cancer via GARP-TGFβ axis. Sci Immunol. 2017;2(11):eaai7911.

55. Metelli A., Wu B.X., Riesenberg B. et al. Thrombin contributes to cancer immune evasion via proteolysis of platelet-bound GARP to activate LTGF-β. Sci Transl Med. 2020;12(525):eaay4860.

56. Huynh L.K., Hipolito C.J., Ten Dijke P. A perspective on the development of TGF-β inhibitors for cancer treatment. Biomolecules. 2019;9(11):743.

57. Kalos M., June C.H. Adoptive T cell transfer for cancer immunotherapy in the era of synthetic biology. Immunity. 2013;39(1):49–60.

58. Labelle M., Begum S., Hynes R.O. Direct signaling between platelets and cancer cells induces an epithelial-mesenchymal-like transition and promotes metastasis. Cancer Cell. 2011;20(5):576–90.

59. Xiong G., Chen J., Zhang G. et al. Hsp47 promotes cancer metastasis by enhancing collagen-dependent cancer cell-platelet interaction. Proc Natl Acad Sci U S A. 2020;117(7):3748–58.

60. Zuo X.-X., Yang Y., Zhang Y. et al. Platelets promote breast cancer cell MCF-7 metastasis by direct interaction: surface integrin α2β1-contactingmediated activation of Wnt-β-catenin pathway. Cell Commun Signal. 2019;17(1):1–15.

61. Steinbrecher K.A., Horowitz N.A., Blevins E.A. et al. Colitis-associated cancer is dependent on the interplay between the hemostatic and inflammatory systems and supported by integrin alpha(M)beta(2) engagement of fibrinogen. Cancer Res. 2010;70(7):2634–43.

62. Andrade S.S., Gouvea I.E., Silva M.C.C. et al. Cathepsin K induces platelet dysfunction and affects cell signaling in breast cancer-molecularly distinct behavior of cathepsin K in breast cancer. BMC Cancer. 2016;16:173.

63. Tang M., Jiang L., Lin Y. et al. Platelet microparticle-mediated transfer of miR-939 to epithelial ovarian cancer cells promotes epithelial to mesenchymal transition. Oncotarget. 2017;8(57):97464–75.

64. Qi C.-L., Wei B., Ye J. et al. P-selectin-mediated platelet adhesion promotes the metastasis of murine melanoma cells. PloS One. 2014;9(3):e91320.

65. Zimmerman G.A. Two by two: the pairings of P-selectin and P-selectin glycoprotein ligand 1. Proc Natl Acad Sci U S A. 2001;98(18):10023–4.

66. Qi Y., Chen W., Liang X. et al. Novel antibodies against GPIbα inhibit pulmonary metastasis by affecting vWF-GPIbα interaction. J Hematol Oncol. 2018;11(1):117.

67. Morimoto K., Satoh-Yamaguchi K., Hamaguchi A. et al. Interaction of cancer cells with platelets mediated by Necl-5/poliovirus receptor enhances cancer cell metastasis to the lungs. Oncogene. 2008;27(3):264–73.

68. Peyruchaud O., Saier L., Leblanc R. Autotaxin implication in cancer metastasis and autoimunne disorders: functional implication of binding autotaxin to the cell surface. Cancers (Basel). 2019;12(1):105.

69. Im J.H., Fu W., Wang H. et al. Coagulation facilitates tumor cell spreading in the pulmonary vasculature during early metastatic colony formation. Cancer Res. 2004;64(23):8613–9.

70. Schumacher D., Strilic B., Sivaraj K.K. et al. Platelet-derived nucleotides promote tumor-cell transendothelial migration and metastasis via P2Y2 receptor. Cancer Cell. 2013;24(1):130–7.

71. Bambace N.M., Levis J.E., Holmes C.E. The effect of P2Y-mediated platelet activation on the release of VEGF and endostatin from platelets. Platelets. 2010;21(2):85–93.

72. Mammadova-Bach E., Gil-Pulido J., Sarukhanyan E. et al. Platelet glycoprotein VI promotes metastasis through interaction with cancer cell–derived galectin-3. Blood. 2020;135(14):1146–60.

73. Chang C.-N., Feng M.-J., Chen Y.-L. et al. p15PAF is an Rb/E2F-regulated S-phase protein essential for DNA synthesis and cell cycle progression. PloS One. 2013;8(4):e61196.

74. Guerrero J.A., Bennett C., van der Weyden L. et al. Gray platelet syndrome: proinflammatory megakaryocytes and α-granule loss cause myelofibrosis and confer metastasis resistance in mice. Blood. 2014;124(24):3624–35.

75. Mammadova-Bach E., Zigrino P., Brucker C. et al. Platelet integrin α6β1 controls lung metastasis through direct binding to cancer cell–derived ADAM9. JCI Insight. 2016;1(14):e88245.

76. Yu L.-X., Yan L., Yang W. et al. Platelets promote tumour metastasis via interaction between TLR4 and tumour cell-released high-mobility group box1 protein. Nat Commun. 2014;5:52–6.

77. Li R., Ren M., Chen N. et al. Presence of intratumoral platelets is associated with tumor vessel structure and metastasis. BMC Cancer. 2014;14:167.

78. Liu Y, Cao X. Characteristics and significance of the pre-metastatic niche. Cancer Cell. 2016;30(5):668–81.

79. Labelle M., Begum S., Hynes R.O. Platelets guide the formation of early metastatic niches. Proc Natl Acad Sci U S A. 2014;111(30):E3053–61.

80. Lucotti S., Cerutti C., Soyer M. et al. Aspirin blocks formation of metastatic intravascular niches by inhibiting platelet-derived COX-1/thromboxane A2. J Clin Invest. 2019;129(5):1845–62.

81. Catena R., Bhattacharya N., El Rayes T. et al. Bone marrow–derived Gr1+ cells can generate a metastasis-resistant microenvironment via induced secretion of thrombospondin-1. Cancer Discov. 2013;3(5):578–89.

82. Kerr B.A., Harris K.S., Shi L. et al. Platelet TSP-1 controls prostate cancerinduced osteoclast differentiation and bone marrow-derived cell mobilization through TGFβ-1. Am J Clin Exp Urol. 2021;9(1):18–31.

83. De Arcangelis A., Hamade H., Alpy F. et al. Hemidesmosome integrity protects the colon against colitis and colorectal cancer. Gut. 2017;66(10):1748–60.

84. Durrant T.N., van den Bosch M.T., Hers I. Integrin αIIbβ3 outside-in signaling. Blood. 2017;130(14):1607–19.

85. Boucharaba A., Serre C.-M., Grès S. et al. Platelet-derived lysophosphatidic acid supports the progression of osteolytic bone metastases in breast cancer. J Clin Invest. 2004;114(12):1714–25.

86. Echtler K., Konrad I., Lorenz M. et al. Platelet GPIIb supports initial pulmonary retention but inhibits subsequent proliferation of melanoma cells during hematogenic metastasis. PloS One. 2017;12(3):e0172788.

87. Tímar J., Tovari J., Raso E. et al. Platelet-mimicry of cancer cells: epiphenomenon with clinical significance. Oncology. 2005;69(3):185–201.

88. Zhu G., Zhang Q., Reddy E.C. et al. The integrin PSI domain has an endogenous thiol isomerase function and is a novel target for antiplatelet therapy. Blood. 2017;129(13):1840–54.

89. Jain S., Zuka M., Liu J. et al. Platelet glycoprotein Ibα supports experimental lung metastasis. Proc Natl Acad Sci U S A. 2007;104(21):9024–8.

90. Erpenbeck L., Nieswandt B., Schön M. et al. Inhibition of platelet GPIb alpha and promotion of melanoma metastasis. J Invest Dermatol. 2010;130(2):576–86.

91. Malehmir M., Pfister D., Gallage S. et al. Platelet GPIbα is a mediator and potential interventional target for NASH and subsequent liver cancer. Nat Med. 2019;25(4):641–55.

92. Ungerer M., Rosport K., Bültmann A. et al. Novel antiplatelet drug revacept (Dimeric Glycoprotein VI-Fc) specifically and efficiently inhibited collageninduced platelet aggregation without affecting general hemostasis in humans. Circulation. 2011;123(17):1891–9.

93. Kato Y., Kaneko M.K. A cancer-specific monoclonal antibody recognizes the aberrantly glycosylated podoplanin. Sci Rep. 2014;4(1):1–9.

94. Xu M., Wang X., Pan Y. et al. Blocking podoplanin suppresses growth and pulmonary metastasis of human malignant melanoma. BMC Cancer. 2019;19(1):599.

95. Sekiguchi T., Takemoto A., Takagi S. et al. Targeting a novel domain in podoplanin for inhibiting platelet-mediated tumor metastasis. Oncotarget. 2016;7(4):3934.

96. Koki A.T., Masferrer J.L. Celecoxib: a specific COX-2 inhibitor with anticancer properties. Cancer Control. 2002;9(2 Suppl):28–35.

97. Gasic G.J., Gasic T.B., Galanti N. et al. Platelet–tumor–cell interactions in mice. The role of platelets in the spread of malignant disease. Int J Cancer. 1973;11(3):704–18.

98. Kune G.A., Kune S., Watson L.F. Colorectal cancer risk, chronic illnesses, operations and medications: case–control results from the Melbourne Colorectal Cancer Study. 1988. Int J Epidemiol. 2007;36(5):951–7.

99. Benamouzig R., Deyra J., Martin A. et al. Daily soluble aspirin and prevention of colorectal adenoma recurrence: one-year results of the APACC trial. Gastroenterology. 2003;125(2):328–36.

100. Ishikawa H., Wakabayashi K., Suzuki S. et al. Preventive effects of low-dose aspirin on colorectal adenoma growth in patients with familial adenomatous polyposis: double-blind, randomized clinical trial. Cancer Med. 2013;2(1):50–6.

101. Burn J., Gerdes A.-M., Macrae F. et al. Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial. Lancet. 2011;378(9809):2081–7.

102. Frouws M., Bastiaannet E., Langley R. et al. Effect of low-dose aspirin use on survival of patients with gastrointestinal malignancies; an observational study. Br J Cancer. 2017;116(3):405–13.

103. Rothwell P.M., Price J.F., Fowkes F.G.R. et al. 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. 2012;379(9826):1602–12.

104. Lecomte M., Laneuville O., Ji C. et al. Acetylation of human prostaglandin endoperoxide synthase-2 (cyclooxygenase-2) by aspirin. J Biol Chem. 1994;269(18):13207–15.

105. Cazenave J.-P., Gachet C. Anti-platelet drugs: do they affect megakaryocytes? Baillieres Clin Haematol. 1997;10(1):163–80.

106. Lucotti S., Muschel R.J. Platelets and metastasis: new implications of an old interplay. Front Oncol. 2020;10:1350.

107. Gachet C. P2 receptors, platelet function and pharmacological implications. Thromb Haemost. 2008;99(3):466–72.

108. Mezouar S., Darbousset R., Dignat-George F. et al. Inhibition of platelet activation prevents the P-selectin and integrin-dependent accumulation of cancer cell microparticles and reduces tumor growth and metastasis in vivo. Int J Cancer. 2015;136(2):462–75.

109. Gareau A.J., Brien C., Gebremeskel S. et al. Ticagrelor inhibits platelet–tumor cell interactions and metastasis in human and murine breast cancer. Clin Exp Metastasis. 2018;35(1–2):25–35.

110. Cho M.S., Noh K., Haemmerle M. et al. Role of ADP receptors on platelets in the growth of ovarian cancer. Blood. 2017;130(10):1235–42.

111. Geranpayehvaghei M., Shi Q., Zhao B. et al. Targeting delivery of platelets inhibitor to prevent tumor metastasis. Bioconjug Chem. 2019;30(9):2349–57.

112. Elaskalani O., Falasca M., Moran N. et al. The role of platelet-derived ADP and ATP in promoting pancreatic cancer cell survival and gemcitabine resistance. Cancers (Basel). 2017;9(10):142.

113. Denslow A., Switalska M., Jarosz J. et al. Clopidogrel in a combined therapy with anticancer drugs—effect on tumor growth, metastasis, and treatment toxicity: studies in animal models. PLoS One. 2017;12(12):e0188740.

114. Su X., Floyd D.H., Hughes A. et al. The ADP receptor P2RY12 regulates osteoclast function and pathologic bone remodeling. J Clin Invest. 2012;122(10):3579–92.

115. Cheng J.W. Impact of selective platelet inhibition in reducing cardiovascular risk–role of vorapaxar. Vasc Health Risk Manag. 2016;12:263–8.

116. Aisiku O., Peters C.G., De Ceunynck K. et al. Parmodulins inhibit thrombus formation without inducing endothelial injury caused by vorapaxar. Blood. 2015;125(12):1976–85.

117. Ma S.-N., Mao Z.-X., Wu Y. et al. The anti-cancer properties of heparin and its derivatives: a review and prospect. Cell Adhesion & Migration. 2020;14(1):118–28.

118. Azab A.K., Quang P., Azab F. et al. P-selectin glycoprotein ligand regulates the interaction of multiple myeloma cells with the bone marrow microenvironment. Blood. 2012;119(6):1468–78.

119. Gardner R. Crizanlizumab in vaso-occlusive crisis caused by sickle cell disease. Drugs Today (Barc). 2020;56(11):705–14.

120. Peterson J.E., Zurakowski D., Italiano J.E. et al. VEGF, PF4 and PDGF are elevated in platelets of colorectal cancer patients. Angiogenesis. 2012;15(2):265–73.

121. Best M., Sol N., Kooi I. et al. RNA-seq of tumor-educated platelets enables article RNA-seq of tumor-educated platelets enables. Cancer Cell. 2015;28(5):666–76.

122. Best M.G., Wesseling P., Wurdinger T. Tumor-educated platelets as a noninvasive biomarker source for cancer detection and progression monitoring. Cancer Res. 2018;78(13):3407–12.

123. Dai H., Zhou H., Sun Y. et al. D-dimer as a potential clinical marker for predicting metastasis and progression in cancer. Biomed Rep. 2018;9(5):453–7.

124. Geddings J.E., Mackman N. Tumor-derived tissue factor–positive microparticles and venous thrombosis in cancer patients. Blood. 2013;122(11):1873–80.

125. Ibele G.M., Kay N.E., Johnson G.J., Jacob H.S. Human platelets exert cytotoxic effects on tumor cells. Blood. 1985;65(5):1252–5.

126. Sagawa T., Tominaga A., Kodama T., Okada M. Cytotoxicity of unstimulated and thrombin-activated platelets to human tumour cells. Immunology. 1993;78(4):650–6.

127. Ahmad R., Menezes J., Knafo L., Ahmad A. Activated human platelets express Fas-L and induce apoptosis in Fas-positive tumor cells. J Leukoc Biol. 2001;69(1):123–8.

128. Haemmerle M., Taylor M.L., Gutschner T. et al. Platelets reduce anoikis and promote metastasis by activating YAP1 signaling. Nat Commun. 2017;8(1):310.

129. Carr B.I., Cavallini A., D’Alessandro R. et al. Platelet extracts induce growth, migration and invasion in human hepatocellular carcinoma in vitro. BMC Cancer. 2014;14:43.

130. Cho M.S., Bottsford-Miller J., Vasquez H.G. et al. Platelets increase the proliferation of ovarian cancer cells. Blood. 2012;120(24):4869–72.

131. Hu Q., Sun W., Qian C. et al. Anticancer platelet-mimicking nanovehicles. Adv Mater. 2015;27(44):7043–50.

132. Papa A.-L., Jiang A., Korin N. et al. Platelet decoys inhibit thrombosis and prevent metastatic tumor formation in preclinical models. Sci Transl Med. 2019;11(479):eaau5898.

133. Xu P., Zuo H., Zhou R. et al. Doxorubicin-loaded platelets conjugated with anti-CD22 mAbs: a novel targeted delivery system for lymphoma treatment with cardiopulmonary avoidance. Oncotarget. 2017;8(35):58322–37.

134. Haemmerle M., Bottsford-Miller J., Pradeep S. et al. FAK regulates platelet extravasation and tumor growth after antiangiogenic therapy withdrawal. J Clin Invest. 2016;126(5):1885–96.

135. Elaskalani O., Berndt M.C., Falasca M., Metharom P. Targeting platelets for the treatment of cancer. Cancers (Basel). 2017;9(7):94.


For citation:

Slukhanchuk E.V., Bitsadze V.O., Khizroeva J.K., Tretyakova M.V., Solopova A.G., Galkin V.N., Shkoda A.S., Tsibizova V.I., Linnikov V.I., Elalamy I., Gris J., Brenner B., Makatsariya A.D. Platelets, thrombo-inflammation and cancer. Obstetrics, Gynecology and Reproduction. 2021;15(6):755-776.

Views: 74

ISSN 2313-7347 (Print)
ISSN 2500-3194 (Online)