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Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2018

Open Access 01-12-2018 | Review

Role of platelets and platelet receptors in cancer metastasis

Author: Martin Schlesinger

Published in: Journal of Hematology & Oncology | Issue 1/2018

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Abstract

The interaction of tumor cells with platelets is a prerequisite for successful hematogenous metastatic dissemination. Upon tumor cell arrival in the blood, tumor cells immediately activate platelets to form a permissive microenvironment. Platelets protect tumor cells from shear forces and assault of NK cells, recruit myeloid cells by secretion of chemokines, and mediate an arrest of the tumor cell platelet embolus at the vascular wall. Subsequently, platelet-derived growth factors confer a mesenchymal-like phenotype to tumor cells and open the capillary endothelium to expedite extravasation in distant organs. Finally, platelet-secreted growth factors stimulate tumor cell proliferation to micrometastatic foci. This review provides a synopsis on the current literature on platelet-mediated effects in cancer metastasis and particularly focuses on platelet adhesion receptors and their role in metastasis. Immunoreceptor tyrosine-based activation motif (ITAM) and hemi ITAM (hemITAM) comprising receptors, especially, glycoprotein VI (GPVI), FcγRIIa, and C-type lectin-like-2 receptor (CLEC-2) are turned in the spotlight since several new mechanisms and contributions to metastasis have been attributed to this family of platelet receptors in the last years.
Literature
1.
Menter DG, Tucker SC, Kopetz S, Sood AK, Crissman JD, Honn KV. Platelets and cancer: a casual or causal relationship: revisited. Cancer Metastasis Rev. 2014;33:231–69.PubMedPubMedCentralCrossRef
2.
Trousseau. Phlegmasia alba dolens. Clin Medicale L’Hotel-Dieu Paris. 2nd ed. Paris: JB Bailliere & Fils; 1865. p. 654–712.
3.
Gasic GJ, Gasic TB, Galanti N, Johnson T, Murphy S. Platelet-tumor-cell interactions in mice. The role of platelets in the spread of malignant disease. Int J Cancer. 1973;11:704–18.PubMedCrossRef
4.
5.
Hilgard P, Heller H, Schmidt CG. The influence of platelet aggregation inhibitors on metastasis formation in mice (3LL). Z Krebsforsch Klin Onkol Cancer Res Clin Oncol. 1976;86:243–50.PubMedCrossRef
6.
Karpatkin S, Pearlstein E. Role of platelets in tumor cell metastases. Ann Intern Med. 1981;95:636–41.PubMedCrossRef
7.
8.
Contursi A, Sacco A, Grande R, Dovizio M, Patrignani P. Platelets as crucial partners for tumor metastasis: from mechanistic aspects to pharmacological targeting. Cell Mol Life Sci. 2017;74:3491–507.PubMedCrossRef
9.
Li N. Platelets in cancer metastasis: to help the “villain” to do evil. Int J Cancer. 2016;138:2078–87.PubMedCrossRef
10.
11.
12.
Luzzi KJ, MacDonald IC, Schmidt EE, Kerkvliet N, Morris VL, Chambers AF, et al. Multistep nature of metastatic inefficiency: dormancy of solitary cells after successful extravasation and limited survival of early micrometastases. Am J Pathol. 1998;153:865–73.PubMedPubMedCentralCrossRef
13.
Nieswandt B, Hafner M, Echtenacher B, Männel DN. Lysis of tumor cells by natural killer cells in mice is impeded by platelets. Cancer Res. 1999;59:1295–300.PubMed
14.
Zucchella M, Dezza L, Pacchiarini L, Meloni F, Tacconi F, Bonomi E, et al. Human tumor cells cultured “in vitro” activate platelet function by producing ADP or thrombin. Haematologica. 1989;74:541–5.PubMed
15.
Aitokallio-Tallberg A, Kärkkäinen J, Pantzar P, Wahlström T, Ylikorkala O. Prostacyclin and thromboxane in breast cancer: relationship between steroid receptor status and medroxyprogesterone acetate. Br J Cancer. 1985;51:671–4.PubMedPubMedCentralCrossRef
16.
Aitokallio-Tallberg AM, Viinikka LU, Ylikorkala RO. Increased synthesis of prostacyclin and thromboxane in human ovarian malignancy. Cancer Res. 1988;48:2396–8.PubMed
17.
Yu L-X, Yan L, Yang W, Wu F-Q, Ling Y, Chen S-Z, et al. Platelets promote tumour metastasis via interaction between TLR4 and tumour cell-released high-mobility group box1 protein. Nat Commun. 2014;5:5256.PubMedCrossRef
18.
Ward Y, Lake R, Faraji F, Sperger J, Martin P, Gilliard C, et al. Platelets promote metastasis via binding tumor CD97 leading to bidirectional signaling that coordinates transendothelial migration. Cell Rep. 2018;23:808–22.PubMedCrossRefPubMedCentral
19.
20.
Adams GN, Rosenfeldt L, Frederick M, Miller W, Waltz D, Kombrinck K, et al. Colon cancer growth and dissemination relies upon thrombin, stromal PAR-1, and fibrinogen. Cancer Res. 2015;75:4235–43.PubMedPubMedCentralCrossRef
21.
Queiroz KCS, Shi K, Duitman J, Aberson HL, Wilmink JW, van Noesel CJM, et al. Protease-activated receptor-1 drives pancreatic cancer progression and chemoresistance. Int J Cancer. 2014;135:2294–304.PubMedCrossRef
22.
Tsopanoglou NE, Maragoudakis ME. On the mechanism of thrombin-induced angiogenesis. Potentiation of vascular endothelial growth factor activity on endothelial cells by up-regulation of its receptors. J Biol Chem. 1999;274:23969–76.PubMedCrossRef
23.
Chen D, Abrahams JM, Smith LM, McVey JH, Lechler RI, Dorling A. Regenerative repair after endoluminal injury in mice with specific antagonism of protease activated receptors on CD34+ vascular progenitors. Blood. 2008;111:4155–64.PubMedCrossRef
24.
Konstantoulaki M, Kouklis P, Malik AB. Protein kinase C modifications of VE-cadherin, p120, and beta-catenin contribute to endothelial barrier dysregulation induced by thrombin. Am J Physiol Lung Cell Mol Physiol. 2003;285:L434–42.PubMedCrossRef
25.
Shao B, Wahrenbrock MG, Yao L, David T, Coughlin SR, Xia L, et al. Carcinoma mucins trigger reciprocal activation of platelets and neutrophils in a murine model of trousseau syndrome. Blood. 2011;118:4015–23.PubMedPubMedCentralCrossRef
26.
Oleksowicz L, Bhagwati N, DeLeon-Fernandez M. Deficient activity of von Willebrand’s factor-cleaving protease in patients with disseminated malignancies. Cancer Res. 1999;59:2244–50.PubMed
27.
Dvorak HF, Quay SC, Orenstein NS, Dvorak AM, Hahn P, Bitzer AM, et al. Tumor shedding and coagulation. Science. 1981;212:923–4.PubMedCrossRef
28.
Auwerda JJA, Yuana Y, Osanto S, de Maat MPM, Sonneveld P, Bertina RM, et al. Microparticle-associated tissue factor activity and venous thrombosis in multiple myeloma. Thromb Haemost. 2011;105:14–20.PubMedCrossRef
29.
Alonso-Escolano D, Strongin AY, Chung AW, Deryugina EI, Radomski MW. Membrane type-1 matrix metalloproteinase stimulates tumour cell-induced platelet aggregation: role of receptor glycoproteins. Br J Pharmacol. 2004;141:241–52.PubMedCrossRef
30.
Melnikova VO, Mourad-Zeidan AA, Lev DC, Bar-Eli M. Platelet-activating factor mediates MMP-2 expression and activation via phosphorylation of cAMP-response element-binding protein and contributes to melanoma metastasis. J Biol Chem. 2006;281:2911–22.PubMedCrossRef
31.
Chew EC, Wallace AC. Demonstration of fibrin in early stages of experimental metastases. Cancer Res. 1976;36:1904–9.PubMed
32.
Palumbo JS, Talmage KE, Massari JV, La Jeunesse CM, Flick MJ, Kombrinck KW, et al. Platelets and fibrin(ogen) increase metastatic potential by impeding natural killer cell-mediated elimination of tumor cells. Blood. 2005;105:178–85.CrossRefPubMed
33.
Palumbo JS, Talmage KE, Massari JV, La Jeunesse CM, Flick MJ, Kombrinck KW, et al. Tumor cell-associated tissue factor and circulating hemostatic factors cooperate to increase metastatic potential through natural killer cell-dependent and-independent mechanisms. Blood. 2007;110:133–41.PubMedPubMedCentralCrossRef
34.
Palumbo JS, Barney KA, Blevins EA, Shaw MA, Mishra A, Flick MJ, et al. Factor XIII transglutaminase supports hematogenous tumor cell metastasis through a mechanism dependent on natural killer cell function. J Thromb Haemost. 2008;6:812–9.PubMedCrossRef
35.
Kopp H-G, Placke T, Salih HR. Platelet-derived transforming growth factor-beta down-regulates NKG2D thereby inhibiting natural killer cell antitumor reactivity. Cancer Res. 2009;69:7775–83.PubMedCrossRef
36.
Placke T, Örgel M, Schaller M, Jung G, Rammensee H-G, Kopp H-G, 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;72:440–8.PubMedCrossRef
37.
Placke T, Salih HR, Kopp H-G. GITR ligand provided by thrombopoietic cells inhibits NK cell antitumor activity. J Immunol. 2012;189:154–60.PubMedCrossRef
38.
Duffau P, Seneschal J, Nicco C, Richez C, Lazaro E, Douchet I, et al. Platelet CD154 potentiates interferon-alpha secretion by plasmacytoid dendritic cells in systemic lupus erythematosus. Sci Transl Med. 2010;2:47ra63.PubMedCrossRef
39.
Haselmayer P, Grosse-Hovest L, von Landenberg P, Schild H, Radsak MP. TREM-1 ligand expression on platelets enhances neutrophil activation. Blood. 2007;110:1029–35.PubMedCrossRef
40.
Xiang B, Zhang G, Guo L, Li X-A, Morris AJ, Daugherty A, et al. Platelets protect from septic shock by inhibiting macrophage-dependent inflammation via the cyclooxygenase 1 signalling pathway. Nat Commun. 2013;4:2657.PubMedCrossRef
41.
Elzey BD, Tian J, Jensen RJ, Swanson AK, Lees JR, Lentz SR, et al. Platelet-mediated modulation of adaptive immunity. A communication link between innate and adaptive immune compartments. Immunity. 2003;19:9–19.PubMedCrossRef
42.
43.
Metelli A, Salem M, Wallace CH, Wu BX, Li A, Li X, et al. Immunoregulatory functions and the therapeutic implications of GARP-TGF-β in inflammation and cancer. J Hematol Oncol. 2018;11:24.PubMedPubMedCentralCrossRef
44.
Haemmerle M, Taylor ML, Gutschner T, Pradeep S, Cho MS, Sheng J, et al. Platelets reduce anoikis and promote metastasis by activating YAP1 signaling. Nat Commun. 2017;8:310.PubMedPubMedCentralCrossRef
45.
Xu XR, Carrim N, Neves MAD, McKeown T, Stratton TW, Coelho RMP, et al. Platelets and platelet adhesion molecules: novel mechanisms of thrombosis and anti-thrombotic therapies. Thromb J. 2016;14:29.PubMedPubMedCentralCrossRef
46.
47.
48.
49.
Kansas GS. Selectins and their ligands: current concepts and controversies. Blood. 1996;88:3259–87.PubMed
50.
McEver RP. Selectin-carbohydrate interactions during inflammation and metastasis. Glycoconj J. 1997;14:585–91.PubMedCrossRef
51.
Palabrica T, Lobb R, Furie BC, Aronovitz M, Benjamin C, Hsu YM, et al. Leukocyte accumulation promoting fibrin deposition is mediated in vivo by P-selectin on adherent platelets. Nature. 1992;359:848–51.PubMedCrossRef
52.
53.
54.
Mannori G, Crottet P, Cecconi O, Hanasaki K, Aruffo A, Nelson RM, et al. Differential colon cancer cell adhesion to E-, P-, and L-selectin: role of mucin-type glycoproteins. Cancer Res. 1995;55:4425–31.PubMed
55.
Burdick MM, Konstantopoulos K. Platelet-induced enhancement of LS174T colon carcinoma and THP-1 monocytoid cell adhesion to vascular endothelium under flow. Am J Physiol Cell Physiol. 2004;287:C539–47.PubMedCrossRef
56.
Ludwig RJ, Boehme B, Podda M, Henschler R, Jager E, Tandi C, et al. Endothelial P-selectin as a target of heparin action in experimental melanoma lung metastasis. Cancer Res. 2004;64:2743–50.PubMedCrossRef
57.
Coupland LA, Chong BH, Parish CR. Platelets and P-selectin control tumor cell metastasis in an organ-specific manner and independently of NK cells. Cancer Res. 2012;72:4662–71.PubMedCrossRef
58.
Becker KA, Beckmann N, Adams C, Hessler G, Kramer M, Gulbins E, et al. Melanoma cell metastasis via P-selectin-mediated activation of acid sphingomyelinase in platelets. Clin Exp Metastasis. 2017;34:25–35.PubMedCrossRef
59.
Qi C, Wei B, Zhou W, Yang Y, Li B, Guo S, et al. P-selectin-mediated platelet adhesion promotes tumor growth. Oncotarget. 2015;6:6584–96.PubMedPubMedCentral
60.
Nolo R, Herbrich S, Rao A, Zweidler-McKay P, Kannan S, Gopalakrishnan V. Targeting P-selectin blocks neuroblastoma growth. Oncotarget. 2017;8:86657–70.PubMedPubMedCentralCrossRef
61.
Läubli H, Spanaus K-S, Borsig L. Selectin-mediated activation of endothelial cells induces expression of CCL5 and promotes metastasis through recruitment of monocytes. Blood. 2009;114:4583–91.PubMedCrossRef
62.
Zuchtriegel G, Uhl B, Puhr-Westerheide D, Pörnbacher M, Lauber K, Krombach F, et al. Platelets guide leukocytes to their sites of extravasation. PLoS Biol. 2016;14:e1002459.PubMedPubMedCentralCrossRef
63.
da Costa Martins PA, van Gils JM, Mol A, Hordijk PL, Zwaginga JJ. Platelet binding to monocytes increases the adhesive properties of monocytes by up-regulating the expression and functionality of beta1 and beta2 integrins. J Leukoc Biol. 2006;79:499–507.PubMedCrossRef
64.
65.
Nieswandt B, Brakebusch C, Bergmeier W, Schulte V, Bouvard D, Mokhtari-Nejad R, et al. Glycoprotein VI but not alpha2beta1 integrin is essential for platelet interaction with collagen. EMBO J. 2001;20:2120–30.PubMedPubMedCentralCrossRef
66.
Pugh N, Simpson AMC, Smethurst PA, de Groot PG, Raynal N, Farndale RW. Synergism between platelet collagen receptors defined using receptor-specific collagen-mimetic peptide substrata in flowing blood. Blood. 2010;115:5069–79.PubMedPubMedCentralCrossRef
67.
Hall CL, Dubyk CW, Riesenberger TA, Shein D, Keller ET, van Golen KL. Type I collagen receptor (alpha2beta1) signaling promotes prostate cancer invasion through RhoC GTPase. Neoplasia. 2008;10:797–803.PubMedPubMedCentralCrossRef
68.
Sottnik JL, Daignault-Newton S, Zhang X, Morrissey C, Hussain MH, Keller ET, et al. Integrin alpha2beta 1 (α2β1) promotes prostate cancer skeletal metastasis. Clin Exp Metastasis. 2013;30:569–78.PubMedCrossRef
69.
Kunicki TJ, Orchekowski R, Annis D, Honda Y. Variability of integrin alpha 2 beta 1 activity on human platelets. Blood. 1993;82:2693–703.PubMed
70.
71.
72.
Thiagarajan P, Kelly K. Interaction of thrombin-stimulated platelets with vitronectin (S-protein of complement) substrate: inhibition by a monoclonal antibody to glycoprotein IIb-IIIa complex. Thromb Haemost. 1988;60:514–7.PubMedCrossRef
73.
Parker CJ, Stone OL, White VF, Bernshaw NJ. Vitronectin (S protein) is associated with platelets. Br J Haematol. 1989;71:245–52.PubMedCrossRef
74.
Grossi IM, Fitzgerald LA, Kendall A, Taylor JD, Sloane BF, Honn KV. Inhibition of human tumor cell induced platelet aggregation by antibodies to platelet glycoproteins Ib and IIb/IIIa. Proc Soc Exp Biol Med. 1987;186:378–83.PubMedCrossRef
75.
Bastida E, Almirall L, Ordinas A. Tumor-cell-induced platelet aggregation is a glycoprotein-dependent and lipoxygenase-associated process. Int J Cancer. 1987;39:760–3.PubMedCrossRef
76.
Clezardin P, Drouin J, Morel-Kopp MC, Hanss M, Kehrel B, Serre CM, et al. Role of platelet membrane glycoproteins Ib/IX and IIb/IIIa, and of platelet alpha-granule proteins in platelet aggregation induced by human osteosarcoma cells. Cancer Res. 1993;53:4695–700.PubMed
77.
Boukerche H, Berthier-Vergnes O, Tabone E, Doré JF, Leung LL, McGregor JL. Platelet-melanoma cell interaction is mediated by the glycoprotein IIb-IIIa complex. Blood. 1989;74:658–63.PubMed
78.
Amirkhosravi A, Mousa SA, Amaya M, Blaydes S, Desai H, Meyer T, et al. Inhibition of tumor cell-induced platelet aggregation and lung metastasis by the oral GpIIb/IIIa antagonist XV454. Thromb Haemost. 2003;90:549–54.PubMed
79.
Amirkhosravi A, Amaya M, Siddiqui F, Biggerstaff JP, Meyer TV, Francis JL. Blockade of GpIIb/IIIa inhibits the release of vascular endothelial growth factor (VEGF) from tumor cell-activated platelets and experimental metastasis. Platelets. 1999;10:285–92.PubMedCrossRef
80.
Engebraaten O, Trikha M, Juell S, Garman-Vik S, Fodstad Ø. Inhibition of in vivo tumour growth by the blocking of host alpha(v)beta3 and alphaII(b)beta3 integrins. Anticancer Res. 2009;29:131–7.PubMed
81.
Lonsdorf AS, Krämer BF, Fahrleitner M, Schönberger T, Gnerlich S, Ring S, et al. Engagement of αIIbβ3 (GPIIb/IIIa) with ανβ3 integrin mediates interaction of melanoma cells with platelets: a connection to hematogenous metastasis. J Biol Chem. 2012;287:2168–78.PubMedCrossRef
82.
Felding-Habermann B, O’Toole TE, Smith JW, Fransvea E, Ruggeri ZM, Ginsberg MH, et al. Integrin activation controls metastasis in human breast cancer. Proc Natl Acad Sci U S A. 2001;98:1853–8.PubMedPubMedCentralCrossRef
83.
Felding-Habermann B, Fransvea E, O’Toole TE, Manzuk L, Faha B, Hensler M. Involvement of tumor cell integrin alpha v beta 3 in hematogenous metastasis of human melanoma cells. Clin Exp Metastasis. 2002;19:427–36.PubMedCrossRef
84.
Nemeth JA, Nakada MT, Trikha M, Lang Z, Gordon MS, Jayson GC, et al. Alpha-v integrins as therapeutic targets in oncology. Cancer Investig. 2007;25:632–46.CrossRef
85.
Mammadova-Bach E, Zigrino P, Brucker C, Bourdon C, Freund M, De Arcangelis A, et al. Platelet integrin α6β1 controls lung metastasis through direct binding to cancer cell-derived ADAM9. JCI Insight. 2016;1:e88245.PubMedPubMedCentralCrossRef
86.
Murphy G. The ADAMs: signalling scissors in the tumour microenvironment. Nat Rev Cancer. 2008;8:929–41.PubMedCrossRef
87.
Berndt MC, Gregory C, Kabral A, Zola H, Fournier D, Castaldi PA. Purification and preliminary characterization of the glycoprotein Ib complex in the human platelet membrane. Eur J Biochem. 1985;151:637–49.PubMedCrossRef
88.
Du X, Beutler L, Ruan C, Castaldi PA, Berndt MC. Glycoprotein Ib and glycoprotein IX are fully complexed in the intact platelet membrane. Blood. 1987;69:1524–7.PubMed
89.
Modderman PW, Admiraal LG, Sonnenberg A, von dem Borne AE. Glycoproteins V and Ib-IX form a noncovalent complex in the platelet membrane. J Biol Chem. 1992;267:364–9.PubMed
90.
Hagen I, Brosstad F, Gogstad GO, Korsmo R, Solum NO. Further studies on the interaction between thrombin and GP Ib using crossed immunoelectrophoresis. Effect of thrombin inhibitors. Thromb Res. 1982;27:549–54.PubMedCrossRef
91.
Romo GM, Dong JF, Schade AJ, Gardiner EE, Kansas GS, Li CQ, et al. The glycoprotein Ib-IX-V complex is a platelet counterreceptor for P-selectin. J Exp Med. 1999;190:803–14.PubMedPubMedCentralCrossRef
92.
Simon DI, Chen Z, Xu H, Li CQ, J f D, McIntire LV, et al. Platelet glycoprotein ibalpha is a counterreceptor for the leukocyte integrin Mac-1 (CD11b/CD18). J Exp Med. 2000;192:193–204.PubMedPubMedCentralCrossRef
93.
Bradford HN, Pixley RA, Colman RW. Human factor XII binding to the glycoprotein Ib-IX-V complex inhibits thrombin-induced platelet aggregation. J Biol Chem. 2000;275:22756–63.PubMedCrossRef
94.
Baglia FA, Badellino KO, Li CQ, Lopez JA, Walsh PN. Factor XI binding to the platelet glycoprotein Ib-IX-V complex promotes factor XI activation by thrombin. J Biol Chem. 2002;277:1662–8.PubMedCrossRef
95.
Berndt MC, Shen Y, Dopheide SM, Gardiner EE, Andrews RK. The vascular biology of the glycoprotein Ib-IX-V complex. Thromb Haemost. 2001;86:178–88.PubMedCrossRef
96.
Canobbio I, Balduini C, Torti M. Signalling through the platelet glycoprotein Ib-V-IX complex. Cell Signal. 2004;16:1329–44.PubMedCrossRef
97.
Lian L, Li W, Li Z-Y, Mao Y-X, Zhang Y-T, Zhao Y-M, et al. Inhibition of MCF-7 breast cancer cell-induced platelet aggregation using a combination of antiplatelet drugs. Oncol Lett. 2013;5:675–80.PubMedCrossRef
98.
Jain S, Zuka M, Liu J, Russell S, Dent J, Guerrero JA, et al. Platelet glycoprotein Ib alpha supports experimental lung metastasis. Proc Natl Acad Sci U S A. 2007;104:9024–8.PubMedPubMedCentralCrossRef
99.
Erpenbeck L, Nieswandt B, Schön M, Pozgajova M, Schön MP. Inhibition of platelet GPIb alpha and promotion of melanoma metastasis. J Invest Dermatol. 2010;130:576–86.PubMedCrossRef
100.
101.
Murdoch C, Muthana M, Coffelt SB, Lewis CE. The role of myeloid cells in the promotion of tumour angiogenesis. Nat Rev Cancer. 2008;8:618–31.PubMedCrossRef
102.
Hiratsuka S, Watanabe A, Aburatani H, Maru Y. Tumour-mediated upregulation of chemoattractants and recruitment of myeloid cells predetermines lung metastasis. Nat Cell Biol. 2006;8:1369–75.PubMedCrossRef
103.
Kim S, Takahashi H, Lin W-W, Descargues P, Grivennikov S, Kim Y, et al. Carcinoma-produced factors activate myeloid cells through TLR2 to stimulate metastasis. Nature. 2009;457:102–6.PubMedPubMedCentralCrossRef
104.
Kaplan RN, Riba RD, Zacharoulis S, Bramley AH, Vincent L, Costa C, et al. VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature. 2005;438:820–7.PubMedPubMedCentralCrossRef
105.
106.
Ponert JM, Schwarz S, Haschemi R, Müller J, Pötzsch B, Bendas G, et al. The mechanisms how heparin affects the tumor cell induced VEGF and chemokine release from platelets to attenuate the early metastatic niche formation. PLoS One. 2018;13:e0191303.PubMedPubMedCentralCrossRef
107.
Borsig L, Wong R, Hynes RO, Varki NM, Varki A. Synergistic effects of L- and P-selectin in facilitating tumor metastasis can involve non-mucin ligands and implicate leukocytes as enhancers of metastasis. Proc Natl Acad Sci U S A. 2002;99:2193–8.PubMedPubMedCentralCrossRef
108.
Qian B-Z, Li J, Zhang H, Kitamura T, Zhang J, Campion LR, et al. CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis. Nature. 2011;475:222–5.PubMedPubMedCentralCrossRef
109.
Zhao L, Lim SY, Gordon-Weeks AN, Tapmeier TT, Im JH, Cao Y, et al. Recruitment of a myeloid cell subset (CD11b/Gr1 mid) via CCL2/CCR2 promotes the development of colorectal cancer liver metastasis. Hepatology. 2013;57:829–39.PubMedCrossRef
110.
Gil-Bernabé AM, Ferjancic S, Tlalka M, Zhao L, Allen PD, Im JH, et al. Recruitment of monocytes/macrophages by tissue factor-mediated coagulation is essential for metastatic cell survival and premetastatic niche establishment in mice. Blood. 2012;119:3164–75.PubMedCrossRef
111.
112.
Schumacher D, Strilic B, Sivaraj KK, Wettschureck N, Offermanns S. Platelet-derived nucleotides promote tumor-cell transendothelial migration and metastasis via P2Y2 receptor. Cancer Cell. 2013;24:130–7.PubMedCrossRef
113.
Coppinger JA, Cagney G, Toomey S, Kislinger T, Belton O, McRedmond JP, et al. Characterization of the proteins released from activated platelets leads to localization of novel platelet proteins in human atherosclerotic lesions. Blood. 2004;103:2096–104.PubMedCrossRef
114.
Mezouar S, Darbousset R, Dignat-George F, Panicot-Dubois L, Dubois C. 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;136:462–75.PubMedCrossRef
115.
Trikha M, Zhou Z, Timar J, Raso E, Kennel M, Emmell E, et al. Multiple roles for platelet GPIIb/IIIa and alphavbeta3 integrins in tumor growth, angiogenesis, and metastasis. Cancer Res. 2002;62:2824–33.PubMed
116.
Bottsford-Miller J, Choi H-J, Dalton HJ, Stone RL, Cho MS, Haemmerle M, et al. Differential platelet levels affect response to taxane-based therapy in ovarian cancer. Clin Cancer Res. 2015;21:602–10.PubMedCrossRef
117.
Battinelli EM, Markens BA, Italiano JE. Release of angiogenesis regulatory proteins from platelet alpha granules: modulation of physiologic and pathologic angiogenesis. Blood. 2011;118:1359–69.PubMedPubMedCentralCrossRef
118.
Möhle R, Green D, Moore MA, Nachman RL, Rafii S. Constitutive production and thrombin-induced release of vascular endothelial growth factor by human megakaryocytes and platelets. Proc Natl Acad Sci U S A. 1997;94:663–8.PubMedPubMedCentralCrossRef
119.
Heldin CH, Westermark B, Wasteson A. Platelet-derived growth factor. Isolation by a large-scale procedure and analysis of subunit composition. Biochem J. 1981;193:907–13.PubMedPubMedCentralCrossRef
120.
Kaplan DR, Chao FC, Stiles CD, Antoniades HN, Scher CD. Platelet alpha granules contain a growth factor for fibroblasts. Blood. 1979;53:1043–52.PubMed
121.
Ben-Ezra J, Sheibani K, Hwang DL, Lev-Ran A. Megakaryocyte synthesis is the source of epidermal growth factor in human platelets. Am J Pathol. 1990;137:755–9.PubMedPubMedCentral
122.
Ma L, Elliott SN, Cirino G, Buret A, Ignarro LJ, Wallace JL. Platelets modulate gastric ulcer healing: role of endostatin and vascular endothelial growth factor release. Proc Natl Acad Sci U S A. 2001;98:6470–5.PubMedPubMedCentralCrossRef
123.
Jurasz P, Alonso D, Castro-Blanco S, Murad F, Radomski MW. Generation and role of angiostatin in human platelets. Blood. 2003;102:3217–23.PubMedCrossRef
124.
Maione TE, Gray GS, Petro J, Hunt AJ, Donner AL, Bauer SI, et al. Inhibition of angiogenesis by recombinant human platelet factor-4 and related peptides. Science. 1990;247:77–9.PubMedCrossRef
125.
126.
Karayiannakis AJ, Syrigos KN, Polychronidis A, Zbar A, Kouraklis G, Simopoulos C, et al. Circulating VEGF levels in the serum of gastric cancer patients. Ann Surg. 2002;236:37–42.PubMedPubMedCentralCrossRef
127.
Karayiannakis AJ, Bolanaki H, Syrigos KN, Asimakopoulos B, Polychronidis A, Anagnostoulis S, et al. Serum vascular endothelial growth factor levels in pancreatic cancer patients correlate with advanced and metastatic disease and poor prognosis. Cancer Lett. 2003;194:119–24.PubMedCrossRef
128.
Verheul HM, Hoekman K, Lupu F, Broxterman HJ, van der Valk P, Kakkar AK, et al. Platelet and coagulation activation with vascular endothelial growth factor generation in soft tissue sarcomas. Clin Cancer Res. 2000;6:166–71.PubMed
129.
Janowska-Wieczorek A, Wysoczynski M, Kijowski J, Marquez-Curtis L, Machalinski B, Ratajczak J, et al. Microvesicles derived from activated platelets induce metastasis and angiogenesis in lung cancer. Int J Cancer. 2005;113:752–60.PubMedCrossRef
130.
Brill A, Dashevsky O, Rivo J, Gozal Y, Varon D. Platelet-derived microparticles induce angiogenesis and stimulate post-ischemic revascularization. Cardiovasc Res. 2005;67:30–8.PubMedCrossRef
131.
Semple JW, Italiano JE, Freedman J. Platelets and the immune continuum. Nat Rev Immunol. 2011;11:264–74.PubMedCrossRef
132.
Chiodoni C, Iezzi M, Guiducci C, Sangaletti S, Alessandrini I, Ratti C, et al. Triggering CD40 on endothelial cells contributes to tumor growth. J Exp Med. 2006;203:2441–50.PubMedPubMedCentralCrossRef
133.
Italiano JE, Richardson JL, Patel-Hett S, Battinelli E, Zaslavsky A, Short S, et al. Angiogenesis is regulated by a novel mechanism: pro- and antiangiogenic proteins are organized into separate platelet alpha granules and differentially released. Blood. 2008;111:1227–33.PubMedPubMedCentralCrossRef
134.
Chatterjee M, Huang Z, Zhang W, Jiang L, Hultenby K, Zhu L, et al. Distinct platelet packaging, release, and surface expression of proangiogenic and antiangiogenic factors on different platelet stimuli. Blood. 2011;117:3907–11.PubMedCrossRef
135.
Bambace NM, Levis JE, Holmes CE. The effect of P2Y-mediated platelet activation on the release of VEGF and endostatin from platelets. Platelets. 2010;21:85–93.PubMedCrossRef
136.
137.
Battinelli EM, Markens BA, Kulenthirarajan RA, Machlus KR, Flaumenhaft R, Italiano JE. Anticoagulation inhibits tumor cell-mediated release of platelet angiogenic proteins and diminishes platelet angiogenic response. Blood. 2014;123:101–12.PubMedPubMedCentralCrossRef
138.
Johnson KE, Forward JA, Tippy MD, Ceglowski JR, El-Husayni S, Kulenthirarajan R, et al. tamoxifen directly inhibits platelet angiogenic potential and platelet-mediated metastasis. Arterioscler Thromb Vasc Biol. 2017;37:664–74.PubMedPubMedCentralCrossRef
139.
Peters CG, Michelson AD, Flaumenhaft R. Granule exocytosis is required for platelet spreading: differential sorting of α-granules expressing VAMP-7. Blood. 2012;120:199–206.PubMedPubMedCentralCrossRef
140.
Gidlöf O, van der Brug M, Ohman J, Gilje P, Olde B, Wahlestedt C, et al. Platelets activated during myocardial infarction release functional miRNA, which can be taken up by endothelial cells and regulate ICAM1 expression. Blood. 2013;121:3908–17 S1–26.PubMedCrossRef
141.
Feng W, Madajka M, Kerr BA, Mahabeleshwar GH, Whiteheart SW, Byzova TV. A novel role for platelet secretion in angiogenesis: mediating bone marrow-derived cell mobilization and homing. Blood. 2011;117:3893–902.PubMedPubMedCentralCrossRef
142.
Colonna M, Samaridis J, Angman L. Molecular characterization of two novel C-type lectin-like receptors, one of which is selectively expressed in human dendritic cells. Eur J Immunol. 2000;30:697–704.PubMedCrossRef
143.
Sobanov Y, Bernreiter A, Derdak S, Mechtcheriakova D, Schweighofer B, Düchler M, et al. A novel cluster of lectin-like receptor genes expressed in monocytic, dendritic and endothelial cells maps close to the NK receptor genes in the human NK gene complex. Eur J Immunol. 2001;31:3493–503.PubMedCrossRef
144.
Suzuki-Inoue K, Fuller GLJ, García A, Eble JA, Pöhlmann S, Inoue O, et al. A novel Syk-dependent mechanism of platelet activation by the C-type lectin receptor CLEC-2. Blood. 2006;107:542–9.PubMedCrossRef
145.
Suzuki-Inoue K, Inoue O, Ozaki Y. Novel platelet activation receptor CLEC-2: from discovery to prospects. J Thromb Haemost. 2011;9(Suppl 1):44–55.PubMedCrossRef
146.
147.
Hughes CE, Sinha U, Pandey A, Eble JA, O’Callaghan CA, Watson SP. Critical role for an acidic amino acid region in platelet signaling by the HemITAM (hemi-immunoreceptor tyrosine-based activation motif) containing receptor CLEC-2 (C-type lectin receptor-2). J Biol Chem. 2013;288:5127–35.PubMedCrossRef
148.
Séverin S, Pollitt AY, Navarro-Nuñez L, Nash CA, Mourão-Sá D, Eble JA, et al. Syk-dependent phosphorylation of CLEC-2: a novel mechanism of hem-immunoreceptor tyrosine-based activation motif signaling. J Biol Chem. 2011;286:4107–16.PubMedCrossRef
149.
150.
Watanabe M, Okochi E, Sugimoto Y, Tsuruo T. Identification of a platelet-aggregating factor of murine colon adenocarcinoma 26: Mr 44,000 membrane protein as determined by monoclonal antibodies. Cancer Res. 1988;48:6411–6.PubMed
151.
Sugimoto Y, Watanabe M, Oh-hara T, Sato S, Isoe T, Tsuruo T. Suppression of experimental lung colonization of a metastatic variant of murine colon adenocarcinoma 26 by a monoclonal antibody 8F11 inhibiting tumor cell-induced platelet aggregation. Cancer Res. 1991;51:921–5.PubMed
152.
Kato Y, Fujita N, Kunita A, Sato S, Kaneko M, Osawa M, et al. Molecular identification of Aggrus/T1alpha as a platelet aggregation-inducing factor expressed in colorectal tumors. J Biol Chem. 2003;278:51599–605.PubMedCrossRef
153.
154.
Suzuki-Inoue K, Kato Y, Inoue O, Kaneko MK, Mishima K, Yatomi Y, et al. Involvement of the snake toxin receptor CLEC-2, in podoplanin-mediated platelet activation, by cancer cells. J Biol Chem. 2007;282:25993–6001.PubMedCrossRef
155.
Christou CM, Pearce AC, Watson AA, Mistry AR, Pollitt AY, Fenton-May AE, et al. Renal cells activate the platelet receptor CLEC-2 through podoplanin. Biochem J. 2008;411:133–40.PubMedCrossRef
156.
Kato Y, Kaneko MK, Kunita A, Ito H, Kameyama A, Ogasawara S, et al. Molecular analysis of the pathophysiological binding of the platelet aggregation-inducing factor podoplanin to the C-type lectin-like receptor CLEC-2. Cancer Sci. 2008;99:54–61.PubMed
157.
Toyoshima M, Nakajima M, Yamori T, Tsuruo T. Purification and characterization of the platelet-aggregating sialoglycoprotein gp44 expressed by highly metastatic variant cells of mouse colon adenocarcinoma 26. Cancer Res. 1995;55:767–73.PubMed
158.
Dang Q, Liu J, Li J, Sun Y. Podoplanin: a novel regulator of tumor invasion and metastasis. Med Oncol. 2014;31:24.PubMedCrossRef
159.
Schacht V, Ramirez MI, Hong Y-K, Hirakawa S, Feng D, Harvey N, et al. T1alpha/podoplanin deficiency disrupts normal lymphatic vasculature formation and causes lymphedema. EMBO J. 2003;22:3546–56.PubMedPubMedCentralCrossRef
160.
Lowe KL, Navarro-Nunez L, Watson SP. Platelet CLEC-2 and podoplanin in cancer metastasis. Thromb Res. 2012;129(Suppl 1):S30–7.PubMedCrossRef
161.
162.
Martín-Villar E, Megías D, Castel S, Yurrita MM, Vilaró S, Quintanilla M. Podoplanin binds ERM proteins to activate RhoA and promote epithelial-mesenchymal transition. J Cell Sci. 2006;119:4541–53.PubMedCrossRef
163.
Ogasawara S, Kaneko MK, Price JE, Kato Y. Characterization of anti-podoplanin monoclonal antibodies: critical epitopes for neutralizing the interaction between podoplanin and CLEC-2. Hybridoma 2005. 2008;27:259–67.PubMed
164.
Nakazawa Y, Takagi S, Sato S, Oh-hara T, Koike S, Takami M, et al. Prevention of hematogenous metastasis by neutralizing mice and its chimeric anti-Aggrus/podoplanin antibodies. Cancer Sci. 2011;102:2051–7.PubMedCrossRef
165.
Kunita A, Kashima TG, Morishita Y, Fukayama M, Kato Y, Tsuruo T, et al. The platelet aggregation-inducing factor aggrus/podoplanin promotes pulmonary metastasis. Am J Pathol. 2007;170:1337–47.PubMedPubMedCentralCrossRef
166.
Takagi S, Sato S, Oh-hara T, Takami M, Koike S, Mishima Y, et al. Platelets promote tumor growth and metastasis via direct interaction between aggrus/podoplanin and CLEC-2. PLoS One. 2013;8:e73609.PubMedPubMedCentralCrossRef
167.
Takagi S, Takemoto A, Takami M, Oh-hara T, Fujita N. Platelets promote osteosarcoma cell growth through activation of the platelet-derived growth factor receptor-Akt signaling axis. Cancer Sci. 2014;105:983–8.PubMedPubMedCentralCrossRef
168.
Takemoto A, Okitaka M, Takagi S, Takami M, Sato S, Nishio M, et al. A critical role of platelet TGF-β release in podoplanin-mediated tumour invasion and metastasis. Sci Rep. 2017;7:42186.PubMedPubMedCentralCrossRef
169.
Labelle M, Begum S, Hynes RO. Direct signaling between platelets and cancer cells induces an epithelial-mesenchymal-like transition and promotes metastasis. Cancer Cell. 2011;20:576–90.PubMedPubMedCentralCrossRef
170.
Chang Y-W, Hsieh P-W, Chang Y-T, Lu M-H, Huang T-F, Chong K-Y, et al. Identification of a novel platelet antagonist that binds to CLEC-2 and suppresses podoplanin-induced platelet aggregation and cancer metastasis. Oncotarget. 2015;6:42733–48.PubMedPubMedCentral
171.
Shirai T, Inoue O, Tamura S, Tsukiji N, Sasaki T, Endo H, et al. C-type lectin-like receptor 2 promotes hematogenous tumor metastasis and prothrombotic state in tumor-bearing mice. J Thromb Haemost. 2017;15:513–25.PubMedCrossRef
172.
May F, Hagedorn I, Pleines I, Bender M, Vögtle T, Eble J, et al. CLEC-2 is an essential platelet-activating receptor in hemostasis and thrombosis. Blood. 2009;114:3464–72.PubMedCrossRef
173.
Lorenz V, Stegner D, Stritt S, Vögtle T, Kiefer F, Witke W, et al. Targeted downregulation of platelet CLEC-2 occurs through Syk-independent internalization. Blood. 2015;125:4069–77.PubMedPubMedCentralCrossRef
174.
175.
Moroi M, Jung SM, Okuma M, Shinmyozu K. A patient with platelets deficient in glycoprotein VI that lack both collagen-induced aggregation and adhesion. J Clin Invest. 1989;84:1440–5.PubMedPubMedCentralCrossRef
176.
Dütting S, Bender M, Nieswandt B. Platelet GPVI: a target for antithrombotic therapy?! Trends Pharmacol Sci. 2012;33:583–90.PubMedCrossRef
177.
Zahid M, Mangin P, Loyau S, Hechler B, Billiald P, Gachet C, et al. The future of glycoprotein VI as an antithrombotic target. J Thromb Haemost. 2012;10:2418–27.PubMedCrossRef
178.
Best D, Senis YA, Jarvis GE, Eagleton HJ, Roberts DJ, Saito T, et al. GPVI levels in platelets: relationship to platelet function at high shear. Blood. 2003;102:2811–8.PubMedCrossRef
179.
Protty MB, Watkins NA, Colombo D, Thomas SG, Heath VL, Herbert JMJ, et al. Identification of Tspan9 as a novel platelet tetraspanin and the collagen receptor GPVI as a component of tetraspanin microdomains. Biochem J. 2009;417:391–400.PubMedCrossRef
180.
Haining EJ, Matthews AL, Noy PJ, Romanska HM, Harris HJ, Pike J, et al. Tetraspanin Tspan9 regulates platelet collagen receptor GPVI lateral diffusion and activation. Platelets. 2017;28:629–42.PubMedCrossRef
181.
Loyau S, Dumont B, Ollivier V, Boulaftali Y, Feldman L, Ajzenberg N, et al. Platelet glycoprotein VI dimerization, an active process inducing receptor competence, is an indicator of platelet reactivity. Arterioscler Thromb Vasc Biol. 2012;32:778–85.PubMedCrossRef
182.
Poulter NS, Pollitt AY, Owen DM, Gardiner EE, Andrews RK, Shimizu H, et al. Clustering of glycoprotein VI (GPVI) dimers upon adhesion to collagen as a mechanism to regulate GPVI signaling in platelets. J Thromb Haemost. 2017;15:549–64.PubMedPubMedCentralCrossRef
183.
Watson SP, Auger JM, McCarty OJT, Pearce AC. GPVI and integrin alphaIIb beta3 signaling in platelets. J Thromb Haemost. 2005;3:1752–62.PubMedCrossRef
184.
Hughes CE, Auger JM, McGlade J, Eble JA, Pearce AC, Watson SP. Differential roles for the adapters gads and LAT in platelet activation by GPVI and CLEC-2. J Thromb Haemost. 2008;6:2152–9.PubMedPubMedCentralCrossRef
185.
Kato K, Kanaji T, Russell S, Kunicki TJ, Furihata K, Kanaji S, et al. The contribution of glycoprotein VI to stable platelet adhesion and thrombus formation illustrated by targeted gene deletion. Blood. 2003;102:1701–7.PubMedCrossRef
186.
Konstantinides S, Ware J, Marchese P, Almus-Jacobs F, Loskutoff DJ, Ruggeri ZM. Distinct antithrombotic consequences of platelet glycoprotein Ibalpha and VI deficiency in a mouse model of arterial thrombosis. J Thromb Haemost. 2006;4:2014–21.PubMedCrossRef
187.
Jain S, Russell S, Ware J. Platelet glycoprotein VI facilitates experimental lung metastasis in syngenic mouse models. J Thromb Haemost. 2009;7:1713–7.PubMedCrossRef
188.
Dovizio M, Maier TJ, Alberti S, Di Francesco L, Marcantoni E, Münch G, et al. Pharmacological inhibition of platelet-tumor cell cross-talk prevents platelet-induced overexpression of cyclooxygenase-2 in HT29 human colon carcinoma cells. Mol Pharmacol. 2013;84:25–40.PubMedCrossRef
189.
Mani SA, Guo W, Liao M-J, Eaton EN, Ayyanan A, Zhou AY, et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 2008;133:704–15.PubMedPubMedCentralCrossRef
190.
191.
Scheel C, Eaton EN, Li SH-J, Chaffer CL, Reinhardt F, Kah K-J, et al. Paracrine and autocrine signals induce and maintain mesenchymal and stem cell states in the breast. Cell. 2011;145:926–40.PubMedPubMedCentralCrossRef
192.
Berndt MC, Metharom P, Andrews RK. Primary haemostasis: newer insights. Haemophilia. 2014;20(Suppl 4):15–22.PubMedCrossRef
193.
Bültmann A, Li Z, Wagner S, Peluso M, Schönberger T, Weis C, et al. Impact of glycoprotein VI and platelet adhesion on atherosclerosis--a possible role of fibronectin. J Mol Cell Cardiol. 2010;49:532–42.PubMedCrossRef
194.
Alshehri OM, Hughes CE, Montague S, Watson SK, Frampton J, Bender M, et al. Fibrin activates GPVI in human and mouse platelets. Blood. 2015;126:1601–8.PubMedPubMedCentralCrossRef
195.
Inoue O, Suzuki-Inoue K, McCarty OJT, Moroi M, Ruggeri ZM, Kunicki TJ, et al. Laminin stimulates spreading of platelets through integrin alpha6beta1-dependent activation of GPVI. Blood. 2006;107:1405–12.PubMedPubMedCentralCrossRef
196.
Barnes NLP, Warnberg F, Farnie G, White D, Jiang W, Anderson E, et al. Cyclooxygenase-2 inhibition: effects on tumour growth, cell cycling and lymphangiogenesis in a xenograft model of breast cancer. Br J Cancer. 2007;96:575–82.PubMedPubMedCentralCrossRef
197.
Kubo H, Hosono K, Suzuki T, Ogawa Y, Kato H, Kamata H, et al. Host prostaglandin EP3 receptor signaling relevant to tumor-associated lymphangiogenesis. Biomed Pharmacother. 2010;64:101–6.PubMedCrossRef
198.
Hosono K, Suzuki T, Tamaki H, Sakagami H, Hayashi I, Narumiya S, et al. Roles of prostaglandin E2-EP3/EP4 receptor signaling in the enhancement of lymphangiogenesis during fibroblast growth factor-2-induced granulation formation. Arterioscler Thromb Vasc Biol. 2011;31:1049–58.PubMedCrossRef
199.
Shen J, Pavone A, Mikulec C, Hensley SC, Traner A, Chang TK, et al. Protein expression profiles in the epidermis of cyclooxygenase-2 transgenic mice by 2-dimensional gel electrophoresis and mass spectrometry. J Proteome Res. 2007;6:273–86.PubMedCrossRef
200.
Arman M, Krauel K. Human platelet IgG Fc receptor FcγRIIA in immunity and thrombosis. J Thromb Haemost. 2015;13:893–908.PubMedCrossRef
201.
202.
Boulaftali Y, Hess PR, Kahn ML, Bergmeier W. Platelet immunoreceptor tyrosine-based activation motif (ITAM) signaling and vascular integrity. Circ Res. 2014;114:1174–84.PubMedPubMedCentralCrossRef
203.
Stegner D, Haining EJ, Nieswandt B. Targeting glycoprotein VI and the immunoreceptor tyrosine-based activation motif signaling pathway. Arterioscler Thromb Vasc Biol. 2014;34:1615–20.PubMedCrossRef
204.
Mitrugno A, Williams D, Kerrigan SW, Moran N. A novel and essential role for FcγRIIa in cancer cell-induced platelet activation. Blood. 2014;123:249–60.PubMedCrossRef
205.
Zhi H, Rauova L, Hayes V, Gao C, Boylan B, Newman DK, et al. Cooperative integrin/ITAM signaling in platelets enhances thrombus formation in vitro and in vivo. Blood. 2013;121:1858–67.PubMedPubMedCentralCrossRef
Metadata
Title
Role of platelets and platelet receptors in cancer metastasis
Author
Martin Schlesinger
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2018
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-018-0669-2

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