Proceedings of the 12th International Conference on Thrombosis and Hemostasis Issues in Cancer, 2024
Vol. 3 No. s1 (2024)
Coagulome and tumor microenvironment: impact of oncogenes, cellular heterogeneity and extracellular vesicles
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Received: 8 January 2024
Accepted: 22 March 2024
Accepted: 22 March 2024
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Cancer-associated thrombosis (CAT) results from the hemostatic system being dysregulated by the progression of cancer. Despite common clinical manifestations, the mechanisms of CAT may vary greatly because cancers develop along distinct biological trajectories that are imposed by the interaction between the tumor cell genome, the epigenome, the surrounding microenvironment, and the tissue of origin. The coagulome, or repertoire of coagulation effectors, expressed by stromal, inflammatory, and cancer cells at the tumor-vascular interface and systemically, reflects this biological variability. Complex landscapes of coagulant and non-coagulant cellular populations are revealed by single-cell RNA sequencing analyses conducted on unperturbed human cancer tissues. Additionally, through mediators of cell-cell interactions, soluble coagulants, and extracellular vesicles containing tissue factor, podoplanin, and other effectors, coagulomes are projected into the pericellular milieu and systemic circulation. As this complexity is currently outside of the clinical paradigm, one could argue that better CAT management could result from a more individualized analysis of coagulomes in cancer patients.
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Folkman J. Angiogenesis: an organizing principle for drug discovery? Nat Rev Drug Discov 2007;6:273-86. DOI: https://doi.org/10.1038/nrd2115
Jain RK, Di TE, Duda DG, et al. Angiogenesis in brain tumors. Nat Rev Neurosci 2007;8:610-22. DOI: https://doi.org/10.1038/nrn2175
Rak J. Ras oncogenes and tumor vascular interface. In: Thomas-Tikhonenko A. (eds.), Cancer Genome and Tumor Microenvironment, Springer, New York, 2009:133-65. DOI: https://doi.org/10.1007/978-1-4419-0711-0_7
Kuczynski EA, Vermeulen PB, Pezzella F, et al. Vessel co-option in cancer. Nat Rev Clin Oncol 2019;16:469-93. DOI: https://doi.org/10.1038/s41571-019-0181-9
Spinelli C, Adnani L, Meehan B, et al. Mesenchymal glioma stem cells trigger vasectasia-distinct neovascularization process stimulated by extracellular vesicles carrying EGFR. Nature Communications 2024;15:2865. DOI: https://doi.org/10.1038/s41467-024-46597-x
Alitalo K. The lymphatic vasculature in disease. Nat Med 2011;17:1371-80. DOI: https://doi.org/10.1038/nm.2545
Ricci-Vitiani L, Pallini R, Biffoni M, et al. Tumor vascularization via endothelial differentiation of glioblastoma stem-like cells. Nature 2010;468:824-8. DOI: https://doi.org/10.1038/nature09557
Allen E, Jabouille A, Rivera LB, et al. Combined antiangiogenic and anti-PD-L1 therapy stimulates tumor immunity through HEV formation. Sci Transl Med 2017;9. DOI: https://doi.org/10.1126/scitranslmed.aak9679
Huinen ZR, Huijbers EJM, van Beijnum JR, et al. Anti-angiogenic agents - overcoming tumor endothelial cell anergy and improving immunotherapy outcomes. Nat Rev Clin Oncol 2021;18:527-40. DOI: https://doi.org/10.1038/s41571-021-00496-y
Rak J, Emmenegger U. Angiogenesis. In: Harrington LA, Tannock IF, Hill RP, Cescon DW. (eds.), The Basic Science of Oncology, 6e, New York (NY):McGraw-Hill Education, 2021.
Khan KA, Kerbel RS. Improving immunotherapy outcomes with anti-angiogenic treatments and vice versa, Nat Rev Clin Oncol 2018;15:310-24. DOI: https://doi.org/10.1038/nrclinonc.2018.9
Ferrara N. VEGF as a therapeutic target in cancer. Oncology 2005;69:11-6. DOI: https://doi.org/10.1159/000088479
Cao Y, Langer R, Ferrara N. Targeting angiogenesis in oncology, ophthalmology and beyond. Nat Rev Drug Discov 2023;22:476-95. DOI: https://doi.org/10.1038/s41573-023-00671-z
Betsholtz C. Cell-cell signaling in blood vessel development and function. EMBO Mol Med 2018;10. DOI: https://doi.org/10.15252/emmm.201708610
De Palma M, Biziato D, Petrova TV. Microenvironmental regulation of tumor angiogenesis, Nat Rev Cancer 2017;17:457-74. DOI: https://doi.org/10.1038/nrc.2017.51
Rak JW, Hegmann EJ, Lu C, Kerbel RS. Progressive loss of sensitivity to endothelium-derived growth inhibitors expressed by human melanoma cells during disease progression. J Cell Physiol 1994;159:245-55. DOI: https://doi.org/10.1002/jcp.1041590208
Adnani L, Kassouf J, Meehan B, et al. Angiocrine extracellular vesicles impose mesenchymal reprogramming upon proneural glioma stem cells. Nat Commun 2022;13:5494. DOI: https://doi.org/10.1038/s41467-022-33235-7
Lu J, Ye X, Fan F, et al. Endothelial Cells Promote the Colorectal Cancer Stem Cell Phenotype through a Soluble Form of Jagged-1. Cancer Cell 2013;23:171-85. DOI: https://doi.org/10.1016/j.ccr.2012.12.021
Nicosia RF, Tchao R, Leighton J. Angiogenesis-dependent tumor spread in reinforced fibrin clot culture. Cancer Res 1983;43:2159-66.
Butler JM, Kobayashi H, Rafii S. Instructive role of the vascular niche in promoting tumor growth and tissue repair by angiocrine factors. Nat Rev Cancer 2010;10:138-46. DOI: https://doi.org/10.1038/nrc2791
Rafii S, Butler JM, Ding BS. Angiocrine functions of organ-specific endothelial cells. Nature 2016;529:316-25. DOI: https://doi.org/10.1038/nature17040
Haemmerle M, Stone RL, Menter DG, Vet al. The Platelet Lifeline to Cancer: Challenges and Opportunities, Cancer Cell 2018;33:965-83. DOI: https://doi.org/10.1016/j.ccell.2018.03.002
Nierodzik ML, Karpatkin S. Thrombin induces tumor growth, metastasis, and angiogenesis: Evidence for a thrombin-regulated dormant tumor phenotype. Cancer Cell 2006;10:355-62. DOI: https://doi.org/10.1016/j.ccr.2006.10.002
Wang G, Li J, Bojmar L, et al. Tumor extracellular vesicles and particles induce liver metabolic dysfunction. Nature 2023;618:374-82. DOI: https://doi.org/10.1038/s41586-023-06114-4
Fong MY, Zhou W, Liu L, et al. Breast-cancer-secreted miR-122 reprograms glucose metabolism in premetastatic niche to promote metastasis. Nat Cell Biol 2015;17:183-94. DOI: https://doi.org/10.1038/ncb3094
Rodrigues G, Hoshino A, Kenific CM, et al. Tumor exosomal CEMIP protein promotes cancer cell colonization in brain metastasis. Nat Cell Biol 2019;21:1403-12. DOI: https://doi.org/10.1038/s41556-019-0404-4
Chen G, Huang AC, Zhang W, et al. Exosomal PD-L1 contributes to immunosuppression and is associated with anti-PD-1 response. Nature 2018;560:382-6. DOI: https://doi.org/10.1038/s41586-018-0392-8
Chitti SV, Fonseka P, Mathivanan S. Emerging role of extracellular vesicles in mediating cancer cachexia. Biochem Soc Trans 2018;46:1129-36. DOI: https://doi.org/10.1042/BST20180213
Khorana AA, Mackman N, Falanga A, et al. Cancer-associated venous thromboembolism. Nat Rev Dis Primers 2022;8:11. DOI: https://doi.org/10.1038/s41572-022-00336-y
Fidler IJ. The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited. Nat Rev Cancer 2003;3: 453-8. DOI: https://doi.org/10.1038/nrc1098
Palumbo JS, Degen JL. Mechanisms linking tumor cell-associated procoagulant function to tumor metastasis. Thromb Res 2007;120:S22-8. DOI: https://doi.org/10.1016/S0049-3848(07)70127-5
Versteeg HH, Spek CA, Peppelenbosch MP, Richel DJ. Tissue factor and cancer metastasis: the role of intracellular and extracellular signaling pathways. Mol Med 2004;10:6-11. DOI: https://doi.org/10.2119/2003-00047.Versteeg
Kaplan RN, Riba RD, Zacharoulis S, et al. VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature 2005;438:820-7. DOI: https://doi.org/10.1038/nature04186
Gil-Bernabe AM, Ferjancic S, Tlalka M, 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. DOI: https://doi.org/10.1182/blood-2011-08-376426
Peinado H, Aleckovic M, Lavotshkin S, et al. Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nat Med 2012;18: 833-91. DOI: https://doi.org/10.1038/nm.2753
Wortzel I, Dror S, Kenific CM, Lyden D. Exosome-Mediated Metastasis: Communication from a Distance. Dev Cell 2019;49:347-60. DOI: https://doi.org/10.1016/j.devcel.2019.04.011
Hisada Y, Mackman N. Cancer-associated pathways and biomarkers of venous thrombosis. Blood 2017;130:1499-506. DOI: https://doi.org/10.1182/blood-2017-03-743211
Tehrani M, Friedman TM, Olson JJ, Brat DJ. Intravascular thrombosis in central nervous system malignancies: a potential role in astrocytoma progression to glioblastoma. Brain Pathol 2008;18:164-71. DOI: https://doi.org/10.1111/j.1750-3639.2007.00108.x
Burdett KB, Unruh D, Drumm M, et al. Determining venous thromboembolism risk in patients with adult-type diffuse glioma. Blood 2023;141:1322-36. DOI: https://doi.org/10.1182/blood.2022017858
Jo J, Diaz M, Horbinski C, et al. Epidemiology, biology, and management of venous thromboembolism in gliomas: An interdisciplinary review. Neuro Oncol 2023;25:1381-94. DOI: https://doi.org/10.1093/neuonc/noad059
Unruh D, Schwarze SR, Khoury L, et al. Mutant IDH1 and thrombosis in gliomas. Acta Neuropathol 2016;132:917-30. DOI: https://doi.org/10.1007/s00401-016-1620-7
Timp JF, Braekkan SK, Versteeg HH, Cannegieter SC. Epidemiology of cancer-associated venous thrombosis. Blood 2013;122:1712-23. DOI: https://doi.org/10.1182/blood-2013-04-460121
Trousseau A. Phlegmasia alba dolens. Paris: Clinique Medicale de L’Hotel Dieu de Paris, 1865:654-712.
Rickles FR, Falanga A. Activation of clotting factors in cancer. Cancer Treat Res 2009;148:31-41. DOI: https://doi.org/10.1007/978-0-387-79962-9_3
Ruf W, Disse J, Carneiro-Lobo TC, et al. Tissue factor and cell signalling in cancer progression and thrombosis. J Thromb Haemost 2011;9:306-15. DOI: https://doi.org/10.1111/j.1538-7836.2011.04318.x
Dvorak HF, Quay SC, Orenstein NS, et al. Tumor shedding and coagulation. Science 1981;212:923-4. DOI: https://doi.org/10.1126/science.7195067
Yu JL, May L, Lhotak V, et al. Oncogenic events regulate tissue factor expression in colorectal cancer cells: implications for tumor progression and angiogenesis. Blood 2005;105: 1734-41. DOI: https://doi.org/10.1182/blood-2004-05-2042
Koizume S, Jin MS, Miyagi E, et al. Activation of cancer cell migration and invasion by ectopic synthesis of coagulation factor VII. Cancer Res 2006;66:9453-60. DOI: https://doi.org/10.1158/0008-5472.CAN-06-1803
Boccaccio C, Sabatino G, Medico E, et al. The MET oncogene drives a genetic programme linking cancer to haemostasis. Nature 2005;434:396-400. DOI: https://doi.org/10.1038/nature03357
Riedl J, Preusser M, Nazari PM, et al. Podoplanin expression in primary brain tumors induces platelet aggregation and increases risk of venous thromboembolism. Blood 2017;129: 1831-9. DOI: https://doi.org/10.1182/blood-2016-06-720714
Tawil N, Bassawon R, Meehan B, et al. Glioblastoma cell populations with distinct oncogenic programs release podoplanin as procoagulant extracellular vesicles. Blood Adv 2021;5:1682-94. DOI: https://doi.org/10.1182/bloodadvances.2020002998
Rak J, Yu JL, Luyendyk J, Mackman N. Oncogenes, trousseau syndrome, and cancer-related changes in the coagulome of mice and humans. Cancer Res 2006;66:10643-6. DOI: https://doi.org/10.1158/0008-5472.CAN-06-2350
Magnus N, Gerges N, Jabado N, Rak J. Coagulation-related gene expression profile in glioblastoma is defined by molecular disease subtype. J Thromb Haemost 2013;11:1197-200. DOI: https://doi.org/10.1111/jth.12242
Tawil N, Bassawon R, Rak J. Oncogenes and Clotting Factors: The Emerging Role of Tumor Cell Genome and Epigenome in Cancer-Associated Thrombosis. Semin Thromb Hemost 2019;45:373-84. DOI: https://doi.org/10.1055/s-0039-1687891
Galmiche A, Rak J, Roumenina LT, Saidak Z. Coagulome and the tumor microenvironment: an actionable interplay. Trends Cancer 2022;8:369-83. DOI: https://doi.org/10.1016/j.trecan.2021.12.008
Wun T, White RH. Venous thromboembolism (VTE) in patients with cancer: epidemiology and risk factors, Cancer Invest 2009;27:63-74. DOI: https://doi.org/10.1080/07357900802656681
Buller HR, van Doormaal FF, van Sluis GL, Kamphuisen PW. Cancer and thrombosis: from molecular mechanisms to clinical presentations. J Thromb Haemost 2007;5:246-54. DOI: https://doi.org/10.1111/j.1538-7836.2007.02497.x
Wen PY, Weller M, Lee EQ, et al. Glioblastoma in adults: a Society for Neuro-Oncology (SNO) and European Society of Neuro-Oncology (EANO) consensus review on current management and future directions. Neuro Oncol 2020;22: 1073-113. DOI: https://doi.org/10.1093/neuonc/noaa106
Falanga A, Marchetti M, Vignoli A. Coagulation and cancer: biological and clinical aspects. J Thromb Haemost 2013;11: 223-33. DOI: https://doi.org/10.1111/jth.12075
Kakkar AK, Lemoine NR, Scully MF, et al. Tissue factor expression correlates with histological grade in human pancreatic cancer. Br J Surg 1995;82:1101-4. DOI: https://doi.org/10.1002/bjs.1800820831
Shigemori C, Wada H, Matsumoto K, et al. Tissue factor expression and metastatic potential of colorectal cancer. Thromb Haemost 1998;80:894-8. DOI: https://doi.org/10.1055/s-0037-1615384
Bishop JM. Cancer: the rise of the genetic paradigm. Genes Dev 1995;9:1309-15. DOI: https://doi.org/10.1101/gad.9.11.1309
Rak J, Klement G. Impact of oncogenes and tumor suppressor genes on deregulation of hemostasis and angiogenesis in cancer. Cancer Metastasis Rev 2000;19:93-6. DOI: https://doi.org/10.1023/A:1026516920119
Rong Y, Post DE, Pieper RO, et al. PTEN and hypoxia regulate tissue factor expression and plasma coagulation by glioblastoma. Cancer Res 2005;65:1406-13. DOI: https://doi.org/10.1158/0008-5472.CAN-04-3376
Magnus N, Garnier D, Rak J. Oncogenic epidermal growth factor receptor up-regulates multiple elements of the tissue factor signaling pathway in human glioma cells. Blood 2010;116:815-8. DOI: https://doi.org/10.1182/blood-2009-10-250639
Magnus N, Garnier D, Meehan B, et al. Tissue factor expression provokes escape from tumor dormancy and leads to genomic alterations. Proc Natl Acad Sci USA 2014;111: 3544-9. DOI: https://doi.org/10.1073/pnas.1314118111
Ades S, Kumar S, Alam M, et al. Tumor oncogene (KRAS) status and risk of venous thrombosis in patients with metastatic colorectal cancer. J Thromb Haemost 2015;13:998-1003. DOI: https://doi.org/10.1111/jth.12910
Diaz M, Jo J, Smolkin M, et al. Risk of Venous Thromboembolism in Grade II-IV Gliomas as a Function of Molecular Subtype. Neurology 2021;96:e1063-e1069. DOI: https://doi.org/10.1212/WNL.0000000000011414
Dunbar A, Bolton KL, Devlin SM, et al. Genomic profiling identifies somatic mutations predicting thromboembolic risk in patients with solid tumors. Blood 2021;137:2103-13. DOI: https://doi.org/10.1182/blood.2020007488
Algaze S, Elliott A, Walker P, et al. Tissue factor expression in colorectal cancer. Chicago: ASCO, 2023. DOI: https://doi.org/10.1200/JCO.2023.41.4_suppl.250
Schwartzentruber J, Korshunov A, Liu XY, et al. Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma. Nature 2012;482:226-31. DOI: https://doi.org/10.1038/nature10833
Neftel C, Laffy J, Filbin MG, et al. An integrative model of cellular states, plasticity, and genetics for glioblastoma. Cell 2019;178:835-849.e21. DOI: https://doi.org/10.1016/j.cell.2019.06.024
Milsom C, Anderson GM, Weitz JI, Rak J. Elevated tissue factor procoagulant activity in CD133-positive cancer cells. J Thromb Haemost 2007;5:2550-2. DOI: https://doi.org/10.1111/j.1538-7836.2007.02766.x
Schaffner F, Yokota N, Carneiro-Lobo T, et al. Endothelial protein C receptor function in murine and human breast cancer development. PLoS ONE 2013;8:e61071. DOI: https://doi.org/10.1371/journal.pone.0061071
Unruh D, Mirkov S, Wray B, et al. Methylation-dependent Tissue Factor Suppression Contributes to the Reduced Malignancy of IDH1-mutant Gliomas. Clin Cancer Res 2019; 25:747-59. DOI: https://doi.org/10.1158/1078-0432.CCR-18-1222
D’Asti E, Huang A, Kool M, et al. Tissue Factor Regulation by miR-520g in Primitive Neuronal Brain Tumor Cells: A Possible Link between Oncomirs and the Vascular Tumor Microenvironment. Am J Pathol 2016;186:446-59. DOI: https://doi.org/10.1016/j.ajpath.2015.10.020
Zhang X, Yu H, Lou JR, et al. MicroRNA-19 (miR-19) regulates tissue factor expression in breast cancer cells. J Biol Chem 2011;286:1429-35. DOI: https://doi.org/10.1074/jbc.M110.146530
Sontheimer-Phelps A, Hassell BA, Ingber DE. Modelling cancer in microfluidic human organs-on-chips. Nat Rev Cancer 2019;19:65-81. DOI: https://doi.org/10.1038/s41568-018-0104-6
Ghosh LD, Jain A. The prospects of microphysiological systems in modeling platelet pathophysiology in cancer. Platelets 2023;34:2247489. DOI: https://doi.org/10.1080/09537104.2023.2247489
Tawil N, Mohamadnia S, Rak J. Oncogenes and cancer associated thrombosis: what can we learn from single cell genomics about risks and mechanisms? Front Med 2023. DOI: https://doi.org/10.3389/fmed.2023.1252417
Patel AP, Tirosh I, Trombetta JJ, et al. Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma. Science 2014;20:1396-401. DOI: https://doi.org/10.1126/science.1254257
Couturier CP, Ayyadhury S, Le PU, et al. Single-cell RNA-seq reveals that glioblastoma recapitulates a normal neurodevelopmental hierarchy. Nat Commun 2020;11:3406. DOI: https://doi.org/10.1038/s41467-020-17186-5
Verhaak RG, Hoadley KA, Purdom E, et al. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 2010;19:98-110. DOI: https://doi.org/10.1016/j.ccr.2009.12.020
Koch R, Demant M, Aung T, et al. Populational equilibrium through exosome-mediated Wnt signaling in tumor progression of diffuse large B-cell lymphoma. Blood 2014;123: 2189-98. DOI: https://doi.org/10.1182/blood-2013-08-523886
Suva ML, Rheinbay E, Gillespie SM, et al. Reconstructing and reprogramming the tumor-propagating potential of glioblastoma stem-like cells. Cell 2014;157:580-94. DOI: https://doi.org/10.1016/j.cell.2014.02.030
Wolberg AS, Rosendaal FR, Weitz JI, et al. Venous thrombosis. Nat Rev Dis Primers 2015;1:15006. DOI: https://doi.org/10.1038/nrdp.2015.6
Zhou Y, Tao W, Shen F, et al. The Emerging Role of Neutrophil Extracellular Traps in Arterial, Venous and Cancer-Associated Thrombosis Front Cardiovasc Med 2021;8: 786387. DOI: https://doi.org/10.3389/fcvm.2021.786387
Théry C, Witwer KW, Aikawa E, et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J Extracell Vesicles 2018;7:1535750. DOI: https://doi.org/10.1080/20013078.2018.1535750
Jeppesen DK, Zhang Q, Franklin JL, Coffey RJ. Extracellular vesicles and nanoparticles: emerging complexities. Trends Cell Biol 2023;33:667-81. DOI: https://doi.org/10.1016/j.tcb.2023.01.002
Rak J. Extracellular vesicles - biomarkers and effectors of the cellular interactome in cancer. Front Pharmacol 2013;4:21. DOI: https://doi.org/10.3389/fphar.2013.00021
Al-Nedawi K, Meehan B, Micallef J, Vet al. Intercellular transfer of the oncogenic receptor EGFRvIII by microvesicles derived from tumor cells. Nat Cell Biol 2008;10:619-24. DOI: https://doi.org/10.1038/ncb1725
Adnani L, Spinelli C, Tawil N, Rak J. Role of extracellular vesicles in cancer-specific interactions between tumor cells and the vasculature. Semin Cancer Biol 2022;87:196-213. DOI: https://doi.org/10.1016/j.semcancer.2022.11.003
Hisada Y, Sachetto ATA, Mackman N. Circulating tissue factor-positive extracellular vesicles and their association with thrombosis in different diseases. Immunol Rev 2022;312:61-75. DOI: https://doi.org/10.1111/imr.13106
Tominaga N, Kosaka N, Ono M, et al. Brain metastatic cancer cells release microRNA-181c-containing extracellular vesicles capable of destructing blood-brain barrier. Nat Commun 2015;6:6716. DOI: https://doi.org/10.1038/ncomms7716
Rak J. Microparticles in cancer. Semin Thromb Hemost 2010;36:888-906. DOI: https://doi.org/10.1055/s-0030-1267043
Lacroix R, Dubois C, Leroyer AS, et al. Revisited role of microparticles in arterial and venous thrombosis. J Thromb Haemost 2013;11:24-35. DOI: https://doi.org/10.1111/jth.12268
Zifkos K, Dubois C, Schäfer K. Extracellular Vesicles and Thrombosis: Update on the Clinical and Experimental Evidence. Int J Mol Sci 2021;22. DOI: https://doi.org/10.3390/ijms22179317
Wang JG, Geddings JE, Aleman MM, et al. Tumor-derived tissue factor activates coagulation and enhances thrombosis in a mouse xenograft model of human pancreatic cancer. Blood 2012;19:5543-52. DOI: https://doi.org/10.1182/blood-2012-01-402156
Sartori MT, Della PA, Ballin A, et al. Circulating microparticles of glial origin and tissue factor bearing in high-grade glioma: a potential prothrombotic role. Thromb Haemost 2013;110:378-85. DOI: https://doi.org/10.1160/TH12-12-0957
Thaler J, Ay C, Mackman N, et al. Microparticle-associated tissue factor activity, venous thromboembolism and mortality in pancreatic, gastric, colorectal and brain cancer patients. J Thromb Haemost 2012;10:1363-70. DOI: https://doi.org/10.1111/j.1538-7836.2012.04754.x
Coumans FAW, Brisson AR, Buzas EI, et al. Methodological Guidelines to Study Extracellular Vesicles. Circ Res 2017;120:1632648. DOI: https://doi.org/10.1161/CIRCRESAHA.117.309417
Shao H, Im H, Castro CM, et al. New Technologies for Analysis of Extracellular Vesicles. Chem Rev 2018;118: 1917-50. DOI: https://doi.org/10.1021/acs.chemrev.7b00534
Jalali M, Del Real Mata C, Montermini L, et al. MoS(2)-Plasmonic Nanocavities for Raman Spectra of Single Extracellular Vesicles Reveal Molecular Progression in Glioblastoma. ACS Nano 2023;17:12052-71. DOI: https://doi.org/10.1021/acsnano.2c09222
Choi D, Montermini L, Jeong H, et al. Mapping Subpopulations of Cancer Cell-Derived Extracellular Vesicles and Particles by Nano-Flow Cytometry. ACS Nano 2019;13: 10499-511. DOI: https://doi.org/10.1021/acsnano.9b04480
Supporting Agencies
Canadian Institutes for Health Research (CIHR PJT 183971), Canadian Institutes for Health Research (CIHR PJT 183971), Fondation Charles Bruneau (FCB) and Fondation CIBC, Canada Foundation for Innovation (CFI), Jack Cole Chair in Pediatric Hematology/OncologyHow to Cite
1.
Tawil N, Adnani L, Rak J. Coagulome and tumor microenvironment: impact of oncogenes, cellular heterogeneity and extracellular vesicles. Bleeding Thromb Vascul Biol [Internet]. 2024 May 16 [cited 2026 Jan. 21];3(s1). Available from: https://www.btvb.org/btvb/article/view/109
Copyright (c) 2024 The Author(s)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
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