Blood coagulation and cancer genes

Best Practice & Research Clinical Haematology - Tập 35 - Trang 101349 - 2022
Nadim Tawil1, Janusz Rak1
1McGill University and Research Institute of the McGill University Health Centre, Canada

Tài liệu tham khảo

Vogelstein, 2004, Cancer genes and the pathways they control, Nat Med, 10, 789, 10.1038/nm1087 Hanahan, 2011, Hallmarks of cancer: the next generation, Cell, 144, 646, 10.1016/j.cell.2011.02.013 Trousseau, 1865, Phlegmasia alba dolens, Clinique medicule de l'Hotel-Dieu de Paris, 3, 94 Tawil, 2021, Glioblastoma cell populations with distinct oncogenic programs release podoplanin as procoagulant extracellular vesicles, Blood Adv, 5, 1682, 10.1182/bloodadvances.2020002998 Dunbar, 2020, Genomic profiling identifies somatic mutations predicting thromboembolic risk in patients with solid tumors, Blood, 137, 2103, 10.1182/blood.2020007488 Tawil, 2019, Oncogenes and clotting factors: the emerging role of tumor cell genome and epigenome in cancer-associated thrombosis, Semin Thromb Hemost, 45, 373, 10.1055/s-0039-1687891 Yu, 2005, Oncogenic events regulate tissue factor expression in colorectal cancer cells: implications for tumor progression and angiogenesis, Blood, 105, 1734, 10.1182/blood-2004-05-2042 Falanga, 2017, Mechanisms and risk factors of thrombosis in cancer, Crit Rev Oncol-Hematol, 118, 79, 10.1016/j.critrevonc.2017.08.003 Hisada, 2018, Mouse models of cancer-associated thrombosis, Thromb Res, 164, S48, 10.1016/j.thromres.2017.12.018 Rickles, 2009, 31 Khorana, 2007, Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy, J Thromb Haemostasis, 5, 632, 10.1111/j.1538-7836.2007.02374.x Navi, 2017, Risk of arterial thromboembolism in patients with cancer, J Am Coll Cardiol, 70, 926, 10.1016/j.jacc.2017.06.047 Khorana, 2022, Cancer-associated venous thromboembolism, Nat Rev Dis Prim, 8, 1 Galmiche, 2022, Coagulome and the tumor microenvironment: an actionable interplay, Trends in Cancer, 8, 369, 10.1016/j.trecan.2021.12.008 Blom, 2005, Malignancies, prothrombotic mutations, and the risk of venous thrombosis, JAMA, 293, 715, 10.1001/jama.293.6.715 Ouaïssi, 2015, Impact of venous thromboembolism on the natural history of pancreatic adenocarcinoma, Hepatobiliary Pancreat Dis Int, 14, 436, 10.1016/S1499-3872(15)60397-6 Timp, 2013, Epidemiology of cancer-associated venous thrombosis, Blood, 122, 1712, 10.1182/blood-2013-04-460121 Khorana, 2007, Tissue factor expression, angiogenesis, and thrombosis in pancreatic cancer, Clin Cancer Res, 13, 2870, 10.1158/1078-0432.CCR-06-2351 Adams, 2009, Coagulation cascade and therapeutics update: relevance to nephrology. Part 1: overview of coagulation, thrombophilias and history of anticoagulants, Nephrology, 14, 462, 10.1111/j.1440-1797.2009.01128.x Hisada, 2017, Cancer-associated pathways and biomarkers of venous thrombosis. Blood, The Journal of the American Society of Hematology, 130, 1499 Quail, 2017, Obesity alters the lung myeloid cell landscape to enhance breast cancer metastasis through IL5 and GM-CSF, Nat Cell Biol, 19, 974, 10.1038/ncb3578 Zhou, 2021, The emerging role of neutrophil extracellular traps in arterial, venous and cancer-associated thrombosis, Frontiers in Cardiovascular Medicine, 8, 10.3389/fcvm.2021.786387 Mackman, 2005, Tissue-specific hemostasis in mice, Arterioscler Thromb Vasc Biol, 25, 2273, 10.1161/01.ATV.0000183884.06371.52 Mackman, 2012, New insights into the mechanisms of venous thrombosis, J Clin Invest, 122, 2331, 10.1172/JCI60229 Suzuki-Inoue, 2019, Platelets and cancer-associated thrombosis: focusing on the platelet activation receptor CLEC-2 and podoplanin, Hematology Am Soc Hematol Educ Program. 2019, 175 Menter, 2022, Of vascular defense, hemostasis, cancer, and platelet biology: an evolutionary perspective, Cancer Metastasis Rev, 1 Riedl, 2017, Podoplanin expression in primary brain tumors induces platelet aggregation and increases risk of venous thromboembolism. Blood, The Journal of the American Society of Hematology, 129, 1831 van der Meijden, 2019, Platelet biology and functions: new concepts and clinical perspectives, Nat Rev Cardiol, 16, 166, 10.1038/s41569-018-0110-0 Stone, 2012, Paraneoplastic thrombocytosis in ovarian cancer, N Engl J Med, 366, 610, 10.1056/NEJMoa1110352 Costa, 2019, Intratumoral platelet aggregate formation in a murine preclinical glioma model depends on podoplanin expression on tumor cells, Blood Adv, 3, 1092, 10.1182/bloodadvances.2018015966 Watson, 2021, Thrombotic and bleeding risk of angiogenesis inhibitors in patients with and without malignancy, J Thromb Haemostasis, 19, 1852, 10.1111/jth.15354 Rak, 2006, Is cancer stem cell a cell, or a multicellular unit capable of inducing angiogenesis?, Med Hypotheses, 66, 601, 10.1016/j.mehy.2005.09.004 Geddings, 2013, Tumor-derived tissue factor–positive microparticles and venous thrombosis in cancer patients, Blood, 122, 1873, 10.1182/blood-2013-04-460139 Shim, 2021, Polyphosphate expression by cancer cell extracellular vesicles mediates binding of factor XII and contact activation, Blood advances, 5, 4741, 10.1182/bloodadvances.2021005116 Unlu, 2018, Cancer-associated thrombosis: the search for the holy grail continues, Res Pract Thromb Haemost, 2, 622, 10.1002/rth2.12143 Wun, 2009, Epidemiology of cancer-related venous thromboembolism, Best Pract Res Clin Haematol, 22, 9, 10.1016/j.beha.2008.12.001 Magnus, 2013, Coagulation‐related gene expression profile in glioblastoma is defined by molecular disease subtype, J Thromb Haemostasis, 11, 1197, 10.1111/jth.12242 Tawil, 2018, Single cell coagulomes as constituents of the oncogene-driven coagulant phenotype in brain tumours, Thromb Res, 164, S136, 10.1016/j.thromres.2018.01.021 Magnus, 2010, Oncogenic epidermal growth factor receptor up-regulates multiple elements of the tissue factor signaling pathway in human glioma cells, Blood, 116, 815, 10.1182/blood-2009-10-250639 Koizume, 2006, Activation of cancer cell migration and invasion by ectopic synthesis of coagulation factor VII, Cancer Res, 66, 9453, 10.1158/0008-5472.CAN-06-1803 D'Asti, 2014, Coagulation and angiogenic gene expression profiles are defined by molecular subgroups of medulloblastoma: evidence for growth factor-thrombin cross-talk, J Thromb Haemostasis, 12, 1838, 10.1111/jth.12715 Magnus, 2014, Oncogenes and the coagulation system–forces that modulate dormant and aggressive states in cancer, Thromb Res, 133, S1, 10.1016/S0049-3848(14)50001-1 Perry, 2012, Thromboembolic disease in patients with high-grade glioma, Neuro Oncology, iv73 Tehrani, 2008, Intravascular thrombosis in central nervous system malignancies: a potential role in astrocytoma progression to glioblastoma, Brain Pathol, 18, 164, 10.1111/j.1750-3639.2007.00108.x Unruh, 2016, Mutant IDH1 and thrombosis in gliomas, Acta Neuropathol, 132, 917, 10.1007/s00401-016-1620-7 Wen, 2020, 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, 22, 1073, 10.1093/neuonc/noaa106 Patel, 2014, Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma, Science, 344, 1396, 10.1126/science.1254257 Neftel, 2019, An integrative model of cellular states, plasticity, and genetics for glioblastoma, Cell, 178, 835, 10.1016/j.cell.2019.06.024 Couturier, 2020, Single-cell RNA-seq reveals that glioblastoma recapitulates a normal neurodevelopmental hierarchy, Nat Commun, 11, 3406, 10.1038/s41467-020-17186-5 Spinelli, 2021, Extracellular vesicle mediated vascular pathology in glioblastoma, News Front: Extracellular Vesicles, 247 Rak, 2000, Impact of oncogenes and tumor suppressor genes on deregulation of hemostasis and angiogenesis in cancer, Cancer Metastasis Rev, 19, 93, 10.1023/A:1026516920119 Milsom, 2007, Elevated tissue factor procoagulant activity in CD133-positive cancer cells, J Thromb Haemostasis, 5, 2550, 10.1111/j.1538-7836.2007.02766.x Garnier, 2012, Cancer cells induced to express mesenchymal phenotype release exosome-like extracellular vesicles carrying tissue factor, J Biol Chem, 287, 43565, 10.1074/jbc.M112.401760 Rak, 1995, Mutant ras oncogenes upregulate VEGF/VPF expression: implications for induction and inhibition of tumor angiogenesis, Cancer Res, 55, 4575 Sparmann, 2004, Ras-induced interleukin-8 expression plays a critical role in tumor growth and angiogenesis, Cancer Cell, 6, 447, 10.1016/j.ccr.2004.09.028 Boccaccio, 2005, The MET oncogene drives a genetic programme linking cancer to haemostasis, Nature, 434, 396, 10.1038/nature03357 Rong, 2005, PTEN and hypoxia regulate tissue factor expression and plasma coagulation by glioblastoma, Cancer Res, 65, 1406, 10.1158/0008-5472.CAN-04-3376 Milsom, 2008, Tissue factor regulation by epidermal growth factor receptor and epithelial-to-mesenchymal transitions: effect on tumor initiation and angiogenesis, Cancer Res, 68, 10068, 10.1158/0008-5472.CAN-08-2067 Rong, 2009, Epidermal growth factor receptor and PTEN modulate tissue factor expression in glioblastoma through JunD/activator protein-1 transcriptional activity, Cancer Res, 69, 2540, 10.1158/0008-5472.CAN-08-1547 Belting, 2005, Signaling of the tissue factor coagulation pathway in angiogenesis and cancer, Arterioscler Thromb Vasc Biol, 25, 1545, 10.1161/01.ATV.0000171155.05809.bf Palumbo, 2007, Tumor cell–associated tissue factor and circulating hemostatic factors cooperate to increase metastatic potential through natural killer cell–dependent and–independent mechanisms, Blood, The Journal of the American Society of Hematology, 110, 133 Versteeg, 2008, Inhibition of tissue factor signaling suppresses tumor growth, Blood, 111, 190, 10.1182/blood-2007-07-101048 Morrow, 2018, Positively selected enhancer elements endow osteosarcoma cells with metastatic competence, Nat Med, 24, 176, 10.1038/nm.4475 Versteeg, 2004, Tissue factor and cancer metastasis: the role of intracellular and extracellular signaling pathways, Mol Med, 10, 6, 10.2119/2003-00047.Versteeg Auvergne, 2016, PAR1 inhibition suppresses the self-renewal and growth of A2B5-defined glioma progenitor cells and their derived gliomas in vivo, Oncogene, 35, 3817, 10.1038/onc.2015.452 Xie, 2021, A novel platelet-related gene signature for predicting the prognosis of triple-negative breast cancer, Front Cell Dev Biol, 9 Tawil, 2020, Genetic and epigenetic regulation of cancer coagulome–lessons from heterogeneity of cancer cell populations, Thromb Res, 191, S99, 10.1016/S0049-3848(20)30405-9 Leiva, 2020, Impact of tumor genomic mutations on thrombotic risk in cancer patients, Cancers, 12, 1958, 10.3390/cancers12071958 Ades, 2015, Tumor oncogene (KRAS) status and risk of venous thrombosis in patients with metastatic colorectal cancer, J Thromb Haemostasis, 13, 998, 10.1111/jth.12910 Ortega Morán, 2020, Incidence of venous thromboembolism in patients with colorectal cancer according to oncogenic status, Clin Transl Oncol, 22, 2026, 10.1007/s12094-020-02339-1 Corrales-Rodriguez, 2014, Mutations in NSCLC and their link with lung cancer-associated thrombosis: a case-control study, Thromb Res, 133, 48, 10.1016/j.thromres.2013.10.042 Zer, 2017, ALK-rearranged non–small-cell lung cancer is associated with a high rate of venous thromboembolism, Clin Lung Cancer, 18, 156, 10.1016/j.cllc.2016.10.007 Liu, 2021, High discrepancy in thrombotic events in non-small cell lung cancer patients with different genomic alterations, Transl Lung Cancer Res, 10, 1512, 10.21037/tlcr-20-1290 Alexander, 2016, A systematic review of biomarkers for the prediction of thromboembolism in lung cancer—results, practical issues and proposed strategies for future risk prediction models, Thromb Res, 148, 63, 10.1016/j.thromres.2016.10.020 Sun, 2020, Wild-type IDH1 and mutant IDH1 opposingly regulate podoplanin expression in glioma, Transl Oncol, 13, 10.1016/j.tranon.2020.100758 Dunbar, 2021, Genomic profiling identifies somatic mutations predicting thromboembolic risk in patients with solid tumors. Blood, The Journal of the American Society of Hematology, 137, 2103 Unruh, 2019, Methylation-dependent tissue factor suppression contributes to the reduced malignancy of IDH1-mutant gliomas, Clin Cancer Res, 25, 747, 10.1158/1078-0432.CCR-18-1222 Buijs, 2020, Genes and proteins associated with the risk for cancer-associated thrombosis, Thromb Res, 191, S43, 10.1016/S0049-3848(20)30396-0 Sussman, 2020, RNA expression and risk of venous thromboembolism in lung cancer, Research and Practice in Thrombosis and Haemostasis, 4, 117, 10.1002/rth2.12284 Zaragoza-Huesca, 2022, Identification of thrombosis-related genes in patients with advanced gastric cancer: data from AGAMENON-SEOM registry, Biomedicines, 10, 148, 10.3390/biomedicines10010148 Luck, 2020, A reference map of the human binary protein interactome, Nature, 580, 402, 10.1038/s41586-020-2188-x 2019, Microvesicles and cancer associated thrombosis 2010, Microparticles in cancer Regina, 2008, Tissue factor expression in non-small cell lung cancer: relationship with vascular endothelial growth factor expression, microvascular density, and K-ras mutation, J Thorac Oncol, 3, 689, 10.1097/JTO.0b013e31817c1b21 Ünlü, 2014, Effects of tumor-expressed coagulation factors on cancer progression and venous thrombosis: is there a key factor?, Thromb Res, 133, S76, 10.1016/S0049-3848(14)50013-8 van den Berg, 2012, The relationship between tissue factor and cancer progression: insights from bench and bedside, Blood, 119, 924, 10.1182/blood-2011-06-317685 Izumi, 2000, Tissue factor pathway inhibitor-2 suppresses the production of active matrix metalloproteinase-2 and is down-regulated in cells harboring activated ras oncogenes, FEBS Lett, 481, 31, 10.1016/S0014-5793(00)01902-5 Mazzieri, 2007, A direct link between expression of urokinase plasminogen activator receptor, growth rate and oncogenic transformation in mouse embryonic fibroblasts, Oncogene, 26, 725, 10.1038/sj.onc.1209833 Zhao, 2008, H‐Ras increases urokinase expression and cell invasion in genetically modified human astrocytes through Ras/Raf/MEK signaling pathway, Glia, 56, 917, 10.1002/glia.20667 Jähner, 1991, The stimulation of quiescent rat fibroblasts by v-src and v-fps oncogenic protein-tyrosine kinases leads to the induction of a subset of immediate early genes, Oncogene, 6, 1259 Joanne, 2010, Modulation of the oncogene-dependent tissue factor expression by kinase suppressor of ras 1, Thromb Res, 126, e6, 10.1016/j.thromres.2010.04.014 Yu, 2004, Shedding of tissue factor (TF)‐containing microparticles rather than alternatively spliced TF is the main source of TF activity released from human cancer cells, J Thromb Haemostasis, 2, 2065, 10.1111/j.1538-7836.2004.00972.x Yu, 2004, Oncogenes as regulators of tissue factor expression in cancer: implications for tumor angiogenesis and anti-cancer therapy, Semin Thromb Hemost, 30, 21, 10.1055/s-2004-822968 Date, 2013, Tumour and microparticle tissue factor expression and cancer thrombosis, Thromb Res, 131, 109, 10.1016/j.thromres.2012.11.013 Provençal, 2009, c-Met activation in medulloblastoma induces tissue factor expression and activity: effects on cell migration, Carcinogenesis, 30, 1089, 10.1093/carcin/bgp085 Falanga, 2007, V617F JAK-2 mutation in patients with essential thrombocythemia: relation to platelet, granulocyte, and plasma hemostatic and inflammatory molecules, Exp Hematol, 35, 702, 10.1016/j.exphem.2007.01.053 Regina, 2009, Increased tissue factor expression is associated with reduced survival in non–small cell lung cancer and with mutations of TP53 and PTEN, Clin Chem, 55, 1834, 10.1373/clinchem.2009.123695 D'Asti, 2016, 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, 186, 446, 10.1016/j.ajpath.2015.10.020 Yu, 2013, MicroRNA-19a targets tissue factor to inhibit colon cancer cells migration and invasion, Mol Cell Biochem, 380, 239, 10.1007/s11010-013-1679-6 Zhang, 2011, MicroRNA-19 (miR-19) regulates tissue factor expression in breast cancer cells, J Biol Chem, 286, 1429, 10.1074/jbc.M110.146530 Chuang, 2012, miR-93/106b and their host gene, MCM7, are differentially expressed in leiomyomas and functionally target F3 and IL-8, Mol Endocrinol, 26, 1028, 10.1210/me.2012-1075 Chu, 2014, A novel estrogen receptor-microRNA 190a-PAR-1-pathway regulates breast cancer progression, a finding initially suggested by genome-wide analysis of loci associated with lymph-node metastasis, Hum Mol Genet, 23, 355, 10.1093/hmg/ddt426 Villadsen, 2012, The miR-143/-145 cluster regulates plasminogen activator inhibitor-1 in bladder cancer, Br J Cancer, 106, 366, 10.1038/bjc.2011.520 Zhu, 2014, miR-30b, down-regulated in gastric cancer, promotes apoptosis and suppresses tumor growth by targeting plasminogen activator inhibitor-1, PLoS One, 9, 10.1371/journal.pone.0106049 Botla, 2016, Early epigenetic downregulation of microRNA-192 expression promotes pancreatic cancer progression, Cancer Res, 76, 4149, 10.1158/0008-5472.CAN-15-0390 Wu, 2013, MicroRNA-143 suppresses gastric cancer cell growth and induces apoptosis by targeting COX-2, World J Gastroenterol: WJG, 19, 7758, 10.3748/wjg.v19.i43.7758 Eisenreich, 2016, Regulation of podoplanin expression by microRNA-29b associates with its antiapoptotic effect in angiotensin II-induced injury of human podocytes, J Hypertens, 34, 323, 10.1097/HJH.0000000000000799 Cortez, 2010, miR‐29b and miR‐125a regulate podoplanin and suppress invasion in glioblastoma, Gene Chromosome Cancer, 49, 981, 10.1002/gcc.20808 Shaker, 2020, Breast cancer stromal clotting activation (Tissue Factor and thrombin): a pre‐invasive phenomena that is prognostic in invasion, Cancer Med, 9, 1768, 10.1002/cam4.2748 Al-Samkari, 2020, Impact of ALK rearrangement on venous and arterial thrombotic risk in NSCLC, J Thorac Oncol, 15, 1497, 10.1016/j.jtho.2020.04.033 Chiari, 2020, ROS1-rearranged non–small-cell lung cancer is associated with a high rate of venous thromboembolism: analysis from a phase II, prospective, multicenter, two-arms trial (METROS), Clin Lung Cancer, 21, 15, 10.1016/j.cllc.2019.06.012 Ng, 2019, ROS1 gene rearrangements are associated with an elevated risk of peridiagnosis thromboembolic events, J Thorac Oncol, 14, 596, 10.1016/j.jtho.2018.12.001 Tallman, 2004, Effects of all‐trans retinoic acid or chemotherapy on the molecular regulation of systemic blood coagulation and fibrinolysis in patients with acute promyelocytic leukemia, J Thromb Haemostasis, 2, 1341, 10.1111/j.1538-7836.2004.00787.x Perez-Segura, 2016, BRCA2 gene mutations and coagulation-associated biomarkers, Thromb Haemostasis, 115, 415, 10.1160/th15-06-0520 Bianconi, 2015, Integrin beta-3 genetic variants and risk of venous thromboembolism in colorectal cancer patients, Thromb Res, 136, 865, 10.1016/j.thromres.2015.08.010 Ünlü, 2018, Genes associated with venous thromboembolism in colorectal cancer patients, J Thromb Haemostasis, 16, 293, 10.1111/jth.13926 Aharon, 2009, Microparticles, thrombosis and cancer, Best Pract Res Clin Haematol, 22, 61, 10.1016/j.beha.2008.11.002 Aharon, 2018, Effects of low-and high-dose chemotherapy agents on thrombogenic properties of extracellular vesicles derived from breast cancer cell lines, Thromb Haemostasis, 118, 480, 10.1055/s-0038-1629901 Mathieu, 2019, Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication, Nat Cell Biol, 21, 9, 10.1038/s41556-018-0250-9 van Niel, 2022, Challenges and directions in studying cell–cell communication by extracellular vesicles, Nat Rev Mol Cell Biol, 1 Zhang, 2018, Identification of distinct nanoparticles and subsets of extracellular vesicles by asymmetric flow field-flow fractionation, Nat Cell Biol, 20, 332, 10.1038/s41556-018-0040-4 Zhang, 2021, Supermeres are functional extracellular nanoparticles replete with disease biomarkers and therapeutic targets, Nat Cell Biol, 23, 1240, 10.1038/s41556-021-00805-8 Zarà, 2019, Biology and role of extracellular vesicles (EVs) in the pathogenesis of thrombosis, Int J Mol Sci, 20, 2840, 10.3390/ijms20112840 Wang, 2012, Tumor-derived tissue factor activates coagulation and enhances thrombosis in a mouse xenograft model of human pancreatic cancer. Blood, The Journal of the American Society of Hematology, 119, 5543 Thaler, 2012, Microparticle-associated tissue factor activity, venous thromboembolism and mortality in pancreatic, gastric, colorectal and brain cancer patients, J Thromb Haemostasis, 10, 1363, 10.1111/j.1538-7836.2012.04754.x Bach, 2006, Tissue factor encryption, Arterioscler Thromb Vasc Biol, 26, 456, 10.1161/01.ATV.0000202656.53964.04 Tsimerman, 2011, Involvement of microparticles in diabetic vascular complications, Thromb Haemostasis, 106, 310, 10.1160/TH10-11-0712 Franco, 2020, A new hybrid immunocapture bioassay with improved reproducibility to measure tissue factor-dependent procoagulant activity of microvesicles from body fluids, Thromb Res, 196, 414, 10.1016/j.thromres.2020.09.020 2019, Venous thromboembolism in brain tumors: risk factors, molecular mechanisms, and clinical challenges Watanabe, 2019, Podoplanin expression and IDH-wildtype status predict venous thromboembolism in patients with high-grade gliomas in the early postoperative period, World neurosurgery, 128, e982, 10.1016/j.wneu.2019.05.049 Al-Nedawi, 2008, Intercellular transfer of the oncogenic receptor EGFRvIII by microvesicles derived from tumour cells, Nat Cell Biol, 10, 619, 10.1038/ncb1725 Lee, 2014, Risk factors and prognostic impact of venous thromboembolism in Asian patients with non-small cell lung cancer, Thromb Haemostasis, 111 Montermini, 2015, Inhibition of oncogenic epidermal growth factor receptor kinase triggers release of exosome-like extracellular vesicles and impacts their phosphoprotein and DNA content, J Biol Chem, 290, 24534, 10.1074/jbc.M115.679217 Spinelli, 2018, Molecular subtypes and differentiation programmes of glioma stem cells as determinants of extracellular vesicle profiles and endothelial cell-stimulating activities, J Extracell Vesicles, 7, 10.1080/20013078.2018.1490144