REFERENCES
1. Niel G, Carter DRF, Clayton A, Lambert DW, Raposo G, Vader P. Challenges and directions in studying cell-cell communication by extracellular vesicles. Nat Rev Mol Cell Biol 2022;23:369-82.
2. Mellman I, Emr SD. A Nobel Prize for membrane traffic: vesicles find their journey’s end. J Cell Biol 2013;203:559-61.
3. Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes. Science 2020;367:eaau6977.
4. Nabhan JF, Hu R, Oh RS, Cohen SN, Lu Q. Formation and release of arrestin domain-containing protein 1-mediated microvesicles (ARMMs) at plasma membrane by recruitment of TSG101 protein. Proc Natl Acad Sci U S A 2012;109:4146-51.
5. Bálint Š, Müller S, Fischer R, et al. Supramolecular attack particles are autonomous killing entities released from cytotoxic T cells. Science 2020;368:897-901.
6. D'Acunzo P, Pérez-González R, Kim Y, et al. Mitovesicles are a novel population of extracellular vesicles of mitochondrial origin altered in Down syndrome. Sci Adv 2021;7:eabe5085.
7. Jeppesen DK, Fenix AM, Franklin JL, et al. Reassessment of exosome composition. Cell 2019;177:428-45.e18.
8. Mathieu M, Névo N, Jouve M, et al. Specificities of exosome versus small ectosome secretion revealed by live intracellular tracking of CD63 and CD9. Nat Commun 2021;12:4389.
9. Di Vizio D, Kim J, Hager MH, et al. Oncosome formation in prostate cancer: association with a region of frequent chromosomal deletion in metastatic disease. Cancer Res 2009;69:5601-9.
10. Minciacchi VR, Spinelli C, Reis-Sobreiro M, et al. MYC mediates large oncosome-induced fibroblast reprogramming in prostate cancer. Cancer Res 2017;77:2306-17.
11. Melentijevic I, Toth ML, Arnold ML, et al. C. elegans neurons jettison protein aggregates and mitochondria under neurotoxic stress. Nature 2017;542:367-71.
12. Zhang H, Freitas D, Kim HS, et al. Identification of distinct nanoparticles and subsets of extracellular vesicles by asymmetric flow field-flow fractionation. Nat Cell Biol 2018;20:332-43.
13. Zhang Q, Jeppesen DK, Higginbotham JN, et al. Supermeres are functional extracellular nanoparticles replete with disease biomarkers and therapeutic targets. Nat Cell Biol 2021;23:1240-54.
14. Zhang H, Lyden D. Asymmetric-flow field-flow fractionation technology for exomere and small extracellular vesicle separation and characterization. Nat Protoc 2019;14:1027-53.
15. Wang Q, Lu Q. Plasma membrane-derived extracellular microvesicles mediate non-canonical intercellular NOTCH signaling. Nat Commun 2017;8:709.
16. 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.
17. Lucotti S, Kenific CM, Zhang H, Lyden D. Extracellular vesicles and particles impact the systemic landscape of cancer. EMBO J 2022;41:e109288.
18. Yates AG, Pink RC, Erdbrügger U, et al. In sickness and in health: the functional role of extracellular vesicles in physiology and pathology in vivo: part I: health and normal physiology: part I: health and normal physiology. J Extracell Vesicles 2022;11:e12151.
19. Yates AG, Pink RC, Erdbrügger U, et al. In sickness and in health: the functional role of extracellular vesicles in physiology and pathology in vivo: part II: pathology: part II: pathology. J Extracell Vesicles 2022;11:e12190.
20. Conde I, Shrimpton CN, Thiagarajan P, López JA. Tissue-factor-bearing microvesicles arise from lipid rafts and fuse with activated platelets to initiate coagulation. Blood 2005;106:1604-11.
21. Ratajczak J, Miekus K, Kucia M, et al. Embryonic stem cell-derived microvesicles reprogram hematopoietic progenitors: evidence for horizontal transfer of mRNA and protein delivery. Leukemia 2006;20:847-56.
22. Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 2007;9:654-9.
23. Cai J, Han Y, Ren H, et al. Extracellular vesicle-mediated transfer of donor genomic DNA to recipient cells is a novel mechanism for genetic influence between cells. J Mol Cell Biol 2013;5:227-38.
24. Kitai Y, Kawasaki T, Sueyoshi T, et al. DNA-containing exosomes derived from cancer cells treated with topotecan activate a sting-dependent pathway and reinforce antitumor immunity. J Immunol 2017;198:1649-59.
25. Peinado H, Alečković M, Lavotshkin S, et al. Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nat Med 2012;18:883-91.
26. Hoshino A, Costa-Silva B, Shen TL, et al. Tumour exosome integrins determine organotropic metastasis. Nature 2015;527:329-35.
27. Clancy JW, Zhang Y, Sheehan C, D'Souza-Schorey C. An ARF6-Exportin-5 axis delivers pre-miRNA cargo to tumour microvesicles. Nat Cell Biol 2019;21:856-66.
28. Clancy JW, Sheehan CS, Boomgarden AC, D'Souza-Schorey C. Recruitment of DNA to tumor-derived microvesicles. Cell Rep 2022;38:110443.
29. Tkach M, Théry C. Communication by extracellular vesicles: where we are and where we need to go. Cell 2016;164:1226-32.
30. Xu R, Rai A, Chen M, Suwakulsiri W, Greening DW, Simpson RJ. Extracellular vesicles in cancer-implications for future improvements in cancer care. Nat Rev Clin Oncol 2018;15:617-38.
31. Al-Nedawi K, Meehan B, Micallef J, et al. Intercellular transfer of the oncogenic receptor EGFRvIII by microvesicles derived from tumour cells. Nat Cell Biol 2008;10:619-24.
32. Demory Beckler M, Higginbotham JN, Franklin JL, et al. Proteomic analysis of exosomes from mutant KRAS colon cancer cells identifies intercellular transfer of mutant KRAS. Mol Cell Proteomics 2013;12:343-55.
33. Qu L, Ding J, Chen C, et al. Exosome-transmitted lncARSR promotes sunitinib resistance in renal cancer by acting as a competing endogenous RNA. Cancer Cell 2016;29:653-68.
34. Chen X, Zhou J, Li X, Wang X, Lin Y, Wang X. Exosomes derived from hypoxic epithelial ovarian cancer cells deliver microRNAs to macrophages and elicit a tumor-promoted phenotype. Cancer Lett 2018;435:80-91.
35. Ma R, Ji T, Chen D, et al. Tumor cell-derived microparticles polarize M2 tumor-associated macrophages for tumor progression. Oncoimmunology 2016;5:e1118599.
36. Skog J, Würdinger T, van Rijn S, et al. Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol 2008;10:1470-6.
37. Luga V, Zhang L, Viloria-Petit AM, et al. Exosomes mediate stromal mobilization of autocrine Wnt-PCP signaling in breast cancer cell migration. Cell 2012;151:1542-56.
38. Butler MT, Wallingford JB. Planar cell polarity in development and disease. Nat Rev Mol Cell Biol 2017;18:375-88.
40. Nusse R, Clevers H. Wnt/β-catenin signaling, disease, and emerging therapeutic modalities. Cell 2017;169:985-99.
41. Endo M, Nishita M, Fujii M, Minami Y. Insight into the role of Wnt5a-induced signaling in normal and cancer cells. International review of cell and molecular biology. Elsevier; 2015. pp. 117-48.
42. Enomoto M, Hayakawa S, Itsukushima S, et al. Autonomous regulation of osteosarcoma cell invasiveness by Wnt5a/Ror2 signaling. Oncogene 2009;28:3197-208.
43. Liu Y, Lu LL, Wen D, et al. MiR-612 regulates invadopodia of hepatocellular carcinoma by HADHA-mediated lipid reprogramming. J Hematol Oncol 2020;13:12.
44. Williams BB, Mundell N, Dunlap J, Jessen J. The planar cell polarity protein VANGL2 coordinates remodeling of the extracellular matrix. Commun Integr Biol 2012;5:325-8.
45. Hoshino D, Kirkbride KC, Costello K, et al. Exosome secretion is enhanced by invadopodia and drives invasive behavior. Cell Rep 2013;5:1159-68.
46. Zöller M. Tetraspanins: push and pull in suppressing and promoting metastasis. Nat Rev Cancer 2009;9:40-55.
47. Hemler ME. Tetraspanin functions and associated microdomains. Nat Rev Mol Cell Biol 2005;6:801-11.
48. Hoshino A, Kim HS, Bojmar L, et al. Extracellular vesicle and particle biomarkers define multiple human cancers. Cell 2020;182:1044-61.e18.
49. Kaplan RN, Riba RD, Zacharoulis S, et al. VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature 2005;438:820-7.
50. Kong J, Tian H, Zhang F, et al. Extracellular vesicles of carcinoma-associated fibroblasts creates a pre-metastatic niche in the lung through activating fibroblasts. Mol Cancer 2019;18:175.
51. Li XQ, Zhang R, Lu H, Yue XM, Huang YF. Extracellular vesicle-packaged CDH11 and ITGA5 induce the premetastatic niche for bone colonization of breast cancer cells. Cancer Res 2022;82:1560-74.
52. Zhou W, Fong MY, Min Y, et al. Cancer-secreted miR-105 destroys vascular endothelial barriers to promote metastasis. Cancer Cell 2014;25:501-15.
53. 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.
54. Ortiz A, Gui J, Zahedi F, et al. An interferon-driven oxysterol-based defense against tumor-derived extracellular vesicles. Cancer Cell 2019;35:33-45.e6.
55. Poggio M, Hu T, Pai CC, et al. Suppression of exosomal PD-L1 induces systemic anti-tumor immunity and memory. Cell 2019;177:414-27.e13.
56. Pucci F, Garris C, Lai CP, et al. SCS macrophages suppress melanoma by restricting tumor-derived vesicle-B cell interactions. Science 2016;352:242-6.
57. Wang T, Wang X, Wang H, et al. High TSPAN8 expression in epithelial cancer cell-derived small extracellular vesicles promote confined diffusion and pronounced uptake. J Extracell Vesicles 2021;10:e12167.
58. Yang C, Dou R, Wei C, et al. Tumor-derived exosomal microRNA-106b-5p activates EMT-cancer cell and M2-subtype TAM interaction to facilitate CRC metastasis. Mol Ther 2021;29:2088-107.
59. Zhang X, Sai B, Wang F, et al. Hypoxic BMSC-derived exosomal miRNAs promote metastasis of lung cancer cells via STAT3-induced EMT. Mol Cancer 2019;18:40.
60. Lööv C, Scherzer CR, Hyman BT, Breakefield XO, Ingelsson M. α-Synuclein in extracellular vesicles: functional implications and diagnostic opportunities. Cell Mol Neurobiol 2016;36:437-48.
61. Melo SA, Sugimoto H, O'Connell JT, et al. Cancer exosomes perform cell-independent microRNA biogenesis and promote tumorigenesis. Cancer Cell 2014;26:707-21.
62. Teng Y, Ren Y, Hu X, et al. MVP-mediated exosomal sorting of miR-193a promotes colon cancer progression. Nat Commun 2017;8:14448.
63. Zhang L, Zhang S, Yao J, et al. Microenvironment-induced PTEN loss by exosomal microRNA primes brain metastasis outgrowth. Nature 2015;527:100-4.
64. Nabet BY, Qiu Y, Shabason JE, et al. Exosome RNA unshielding couples stromal activation to pattern recognition receptor signaling in cancer. Cell 2017;170:352-66.e13.
65. Wu B, Liu DA, Guan L, et al. Stiff matrix induces exosome secretion to promote tumour growth. Nat Cell Biol 2023;25:415-24.
66. Amit M, Takahashi H, Dragomir MP, et al. Loss of p53 drives neuron reprogramming in head and neck cancer. Nature 2020;578:449-54.
67. Magnon C, Hall SJ, Lin J, et al. Autonomic nerve development contributes to prostate cancer progression. Science 2013;341:1236361.
68. Peinado H, Zhang H, Matei IR, et al. Pre-metastatic niches: organ-specific homes for metastases. Nat Rev Cancer 2017;17:302-17.
69. Hirakawa S, Brown LF, Kodama S, Paavonen K, Alitalo K, Detmar M. VEGF-C-induced lymphangiogenesis in sentinel lymph nodes promotes tumor metastasis to distant sites. Blood 2007;109:1010-7.
70. Olmeda D, Cerezo-Wallis D, Riveiro-Falkenbach E, et al. Whole-body imaging of lymphovascular niches identifies pre-metastatic roles of midkine. Nature 2017;546:676-80.
71. Patras L, Shaashua L, Matei I, Lyden D. Immune determinants of the pre-metastatic niche. Cancer Cell 2023;41:546-72.
72. Costa-Silva B, Aiello NM, Ocean AJ, et al. Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver. Nat Cell Biol 2015;17:816-26.
73. García-Silva S, Benito-Martín A, Nogués L, et al. Melanoma-derived small extracellular vesicles induce lymphangiogenesis and metastasis through an NGFR-dependent mechanism. Nat Cancer 2021;2:1387-405.
74. Liu Y, Gu Y, Han Y, et al. Tumor exosomal RNAs promote lung pre-metastatic niche formation by activating alveolar epithelial TLR3 to recruit neutrophils. Cancer Cell 2016;30:243-56.
75. Rodrigues G, Hoshino A, Kenific CM, et al. Tumour exosomal CEMIP protein promotes cancer cell colonization in brain metastasis. Nat Cell Biol 2019;21:1403-12.
76. Paget S. The distribution of secondary growths in cancer of the breast. 1889. Cancer Metastasis Rev 1989;8:98-101.
77. Lengel HB, Mastrogiacomo B, Connolly JG, et al. Genomic mapping of metastatic organotropism in lung adenocarcinoma. Cancer Cell 2023;41:970-985.e3.
78. Mathieu M, Martin-Jaular L, Lavieu G, Théry C. Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication. Nat Cell Biol 2019;21:9-17.
79. Wong GL, Abu Jalboush S, Lo HW. Exosomal microRNAs and organotropism in breast cancer metastasis. Cancers 2020;12:1827.
81. 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.
82. Ye Y, Li SL, Ma YY, et al. Exosomal miR-141-3p regulates osteoblast activity to promote the osteoblastic metastasis of prostate cancer. Oncotarget 2017;8:94834-49.
83. Hashimoto K, Ochi H, Sunamura S, et al. Cancer-secreted hsa-miR-940 induces an osteoblastic phenotype in the bone metastatic microenvironment via targeting ARHGAP1 and FAM134A. Proc Natl Acad Sci U S A 2018;115:2204-9.
84. 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.
85. Wu K, Feng J, Lyu F, et al. Exosomal miR-19a and IBSP cooperate to induce osteolytic bone metastasis of estrogen receptor-positive breast cancer. Nat Commun 2021;12:5196.
86. Zeng Z, Li Y, Pan Y, et al. Cancer-derived exosomal miR-25-3p promotes pre-metastatic niche formation by inducing vascular permeability and angiogenesis. Nat Commun 2018;9:5395.
87. Gupta D, Zickler AM, El Andaloussi S. Dosing extracellular vesicles. Adv Drug Deliv Rev 2021;178:113961.
88. Murillo OD, Thistlethwaite W, Rozowsky J, et al. exRNA atlas analysis reveals distinct extracellular RNA cargo types and their carriers present across human biofluids. Cell 2019;177:463-77.e15.
89. Sato S, Vasaikar S, Eskaros A, et al. EPHB2 carried on small extracellular vesicles induces tumor angiogenesis via activation of ephrin reverse signaling. JCI Insight 2019;4:132447.
90. Metharom P, Falasca M, Berndt MC. The history of armand trousseau and cancer-associated thrombosis. Cancers 2019;11:158.
91. Varki A. Trousseau's syndrome: multiple definitions and multiple mechanisms. Blood 2007;110:1723-9.
92. Dvorak HF, Quay SC, Orenstein NS, et al. Tumor shedding and coagulation. Science 1981;212:923-4.
93. Dvorak HF, Van DeWater L, Bitzer AM, et al. Procoagulant activity associated with plasma membrane vesicles shed by cultured tumor cells. Cancer Res 1983;43:4434-42.
94. Almeida VH, Rondon AMR, Gomes T, Monteiro RQ. Novel aspects of extracellular vesicles as mediators of cancer-associated thrombosis. Cells 2019;8:716.
95. Beck S, Hochreiter B, Schmid JA. Extracellular vesicles linking inflammation, cancer and thrombotic risks. Front Cell Dev Biol 2022;10:859863.
96. Davila M, Amirkhosravi A, Coll E, et al. Tissue factor-bearing microparticles derived from tumor cells: impact on coagulation activation. J Thromb Haemost 2008;6:1517-24.
97. Geddings JE, Mackman N. Tumor-derived tissue factor-positive microparticles and venous thrombosis in cancer patients. Blood 2013;122:1873-80.
98. Hisada Y, Mackman N. Cancer-associated pathways and biomarkers of venous thrombosis. Blood 2017;130:1499-506.
99. Lazar S, Goldfinger LE. Platelets and extracellular vesicles and their cross talk with cancer. Blood 2021;137:3192-200.
100. Lima LG, Leal AC, Vargas G, Porto-Carreiro I, Monteiro RQ. Intercellular transfer of tissue factor via the uptake of tumor-derived microvesicles. Thromb Res 2013;132:450-6.
101. Tesselaar ME, Romijn FP, Van Der Linden IK, Prins FA, Bertina RM, Osanto S. Microparticle-associated tissue factor activity: a link between cancer and thrombosis? J Thromb Haemost 2007;5:520-7.
102. Leal AC, Mizurini DM, Gomes T, et al. Tumor-derived exosomes induce the formation of neutrophil extracellular traps: implications for the establishment of cancer-associated thrombosis. Sci Rep 2017;7:6438.
103. Thålin C, Hisada Y, Lundström S, Mackman N, Wallén H. Neutrophil extracellular traps: villains and targets in arterial, venous, and cancer-associated thrombosis. Arterioscler Thromb Vasc Biol 2019;39:1724-38.
104. Zhao H, Yang L, Baddour J, et al. Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism. Elife 2016;5:e10250.
105. Chen D, Li Y, Wang Y, Xu J. LncRNA HOTAIRM1 knockdown inhibits cell glycolysis metabolism and tumor progression by miR-498/ABCE1 axis in non-small cell lung cancer. Genes Genomics 2021;43:183-94.
106. Ding C, Xi G, Wang G, et al. Exosomal circ-MEMO1 promotes the progression and aerobic glycolysis of non-small cell lung cancer through targeting MiR-101-3p/KRAS axis. Front Genet 2020;11:962.
107. Gong Z, Li Q, Shi J, Liu ET, Shultz LD, Ren G. Lipid-laden lung mesenchymal cells foster breast cancer metastasis via metabolic reprogramming of tumor cells and natural killer cells. Cell Metab 2022;34:1960-76.e9.
108. Ronquist KG, Sanchez C, Dubois L, et al. Energy-requiring uptake of prostasomes and PC3 cell-derived exosomes into non-malignant and malignant cells. J Extracell Vesicles 2016;5:29877.
109. Yan W, Wu X, Zhou W, et al. Cancer-cell-secreted exosomal miR-105 promotes tumour growth through the MYC-dependent metabolic reprogramming of stromal cells. Nat Cell Biol 2018;20:597-609.
110. Zhang J, Lu S, Zhou Y, et al. Motile hepatocellular carcinoma cells preferentially secret sugar metabolism regulatory proteins via exosomes. Proteomics 2017;17:1700103.
111. Cao M, Isaac R, Yan W, et al. Cancer-cell-secreted extracellular vesicles suppress insulin secretion through miR-122 to impair systemic glucose homeostasis and contribute to tumour growth. Nat Cell Biol 2022;24:954-67.
113. Liberti MV, Locasale JW. The warburg effect: how does it benefit cancer cells? Trends Biochem Sci 2016;41:211-8.
114. Rorsman P, Ashcroft FM. Pancreatic β-cell electrical activity and insulin secretion: of mice and men. Physiol Rev 2018;98:117-214.
115. Ostenson CG, Gaisano H, Sheu L, Tibell A, Bartfai T. Impaired gene and protein expression of exocytotic soluble N-ethylmaleimide attachment protein receptor complex proteins in pancreatic islets of type 2 diabetic patients. Diabetes 2006;55:435-40.
116. Gallagher EJ, Zelenko Z, Neel BA, et al. Elevated tumor LDLR expression accelerates LDL cholesterol-mediated breast cancer growth in mouse models of hyperlipidemia. Oncogene 2017;36:6462-71.
117. Hopkins BD, Pauli C, Du X, et al. Suppression of insulin feedback enhances the efficacy of PI3K inhibitors. Nature 2018;560:499-503.
118. Kahn SE, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 2006;444:840-6.
119. Saltiel AR, Olefsky JM. Inflammatory mechanisms linking obesity and metabolic disease. J Clin Invest 2017;127:1-4.
120. Barone BB, Yeh HC, Snyder CF, et al. Long-term all-cause mortality in cancer patients with preexisting diabetes mellitus: a systematic review and meta-analysis. JAMA 2008;300:2754-64.
121. Tsilidis KK, Kasimis JC, Lopez DS, Ntzani EE, Ioannidis JP. Type 2 diabetes and cancer: umbrella review of meta-analyses of observational studies. BMJ 2015;350:g7607.
122. Xu J, Sun Y, Gong D, Fan Y. Impact of preexisting diabetes mellitus on cardiovascular and all-cause mortality in patients with atrial fibrillation: a meta-analysis. Front Endocrinol 2022;13:921159.
123. Dong S, Wang Z, Shen K, Chen X. Metabolic Syndrome and breast cancer: prevalence, treatment response, and prognosis. Front Oncol 2021;11:629666.
124. Peairs KS, Barone BB, Snyder CF, et al. Diabetes mellitus and breast cancer outcomes: a systematic review and meta-analysis. J Clin Oncol 2011;29:40-6.
125. Shahid RK, Ahmed S, Le D, Yadav S. Diabetes and cancer: risk, challenges, management and outcomes. Cancers 2021;13:5735.
126. Wang G, Li J, Bojmar L, et al. Tumour extracellular vesicles and particles induce liver metabolic dysfunction. Nature 2023;618:374-82.
127. Phinney DG, Di Giuseppe M, Njah J, et al. Mesenchymal stem cells use extracellular vesicles to outsource mitophagy and shuttle microRNAs. Nat Commun 2015;6:8472.
128. Sansone P, Savini C, Kurelac I, et al. Packaging and transfer of mitochondrial DNA via exosomes regulate escape from dormancy in hormonal therapy-resistant breast cancer. Proc Natl Acad Sci U S A 2017;114:E9066-75.
130. Yin X, Zeng W, Wu B, et al. PPARα inhibition overcomes tumor-derived exosomal lipid-induced dendritic cell dysfunction. Cell Rep 2020;33:108278.
131. Kim DH, Kim H, Choi YJ, et al. Exosomal PD-L1 promotes tumor growth through immune escape in non-small cell lung cancer. Exp Mol Med 2019;51:1-13.
132. Ricklefs FL, Alayo Q, Krenzlin H, et al. Immune evasion mediated by PD-L1 on glioblastoma-derived extracellular vesicles. Sci Adv 2018;4:eaar2766.
133. Wen SW, Sceneay J, Lima LG, et al. The biodistribution and immune suppressive effects of breast cancer-derived exosomes. Cancer Res 2016;76:6816-27.
134. Jiang Z, Zhang Y, Zhang Y, Jia Z, Zhang Z, Yang J. Cancer derived exosomes induce macrophages immunosuppressive polarization to promote bladder cancer progression. Cell Commun Signal 2021;19:93.
135. Morrissey SM, Zhang F, Ding C, et al. Tumor-derived exosomes drive immunosuppressive macrophages in a pre-metastatic niche through glycolytic dominant metabolic reprogramming. Cell Metab 2021;33:2040-58.e10.
136. Popēna I, Ābols A, Saulīte L, et al. Effect of colorectal cancer-derived extracellular vesicles on the immunophenotype and cytokine secretion profile of monocytes and macrophages. Cell Commun Signal 2018;16:17.
137. Yin Y, Liu B, Cao Y, et al. Colorectal cancer-derived small extracellular vesicles promote tumor immune evasion by upregulating PD-L1 expression in tumor-associated macrophages. Adv Sci 2022;9:2102620.
138. Shin S, Ko H, Kim CH, et al. Curvature-sensing peptide inhibits tumour-derived exosomes for enhanced cancer immunotherapy. Nat Mater 2023;22:656-65.
139. Cheng L, Sharples RA, Scicluna BJ, Hill AF. Exosomes provide a protective and enriched source of miRNA for biomarker profiling compared to intracellular and cell-free blood. J Extracell Vesicles 2014;3:23743.
140. Zhou E, Li Y, Wu F, et al. Circulating extracellular vesicles are effective biomarkers for predicting response to cancer therapy. EBioMedicine 2021;67:103365.
141. Melo SA, Luecke LB, Kahlert C, et al. Glypican-1 identifies cancer exosomes and detects early pancreatic cancer. Nature 2015;523:177-82.
142. McKiernan J, Donovan MJ, O'Neill V, et al. A novel urine exosome gene expression assay to predict high-grade prostate cancer at initial biopsy. JAMA Oncol 2016;2:882-9.
143. Berckmans RJ, Sturk A, van Tienen LM, Schaap MC, Nieuwland R. Cell-derived vesicles exposing coagulant tissue factor in saliva. Blood 2011;117:3172-80.
144. Lässer C, Alikhani VS, Ekström K, et al. Human saliva, plasma and breast milk exosomes contain RNA: uptake by macrophages. J Transl Med 2011;9:9.
145. Herreros-Villanueva M, Bujanda L. Glypican-1 in exosomes as biomarker for early detection of pancreatic cancer. Ann Transl Med 2016;4:64.
146. Yáñez-Mó M, Siljander PR, Andreu Z, et al. Biological properties of extracellular vesicles and their physiological functions. J Extracell Vesicles 2015;4:27066.
147. Øverbye A, Skotland T, Koehler CJ, et al. Identification of prostate cancer biomarkers in urinary exosomes. Oncotarget 2015;6:30357-76.
148. Zhang C, Wang XY, Zhang P, et al. Cancer-derived exosomal HSPC111 promotes colorectal cancer liver metastasis by reprogramming lipid metabolism in cancer-associated fibroblasts. Cell Death Dis 2022;13:57.
149. Sun H, Wang C, Hu B, et al. Exosomal S100A4 derived from highly metastatic hepatocellular carcinoma cells promotes metastasis by activating STAT3. Signal Transduct Target Ther 2021;6:187.
150. Plebanek MP, Angeloni NL, Vinokour E, et al. Pre-metastatic cancer exosomes induce immune surveillance by patrolling monocytes at the metastatic niche. Nat Commun 2017;8:1319.
151. Balaj L, Lessard R, Dai L, et al. Tumour microvesicles contain retrotransposon elements and amplified oncogene sequences. Nat Commun 2011;2:180.
152. Kahlert C, Melo SA, Protopopov A, et al. Identification of double-stranded genomic DNA spanning all chromosomes with mutated KRAS and p53 DNA in the serum exosomes of patients with pancreatic cancer. J Biol Chem 2014;289:3869-75.
153. Thakur BK, Zhang H, Becker A, et al. Double-stranded DNA in exosomes: a novel biomarker in cancer detection. Cell Res 2014;24:766-9.
154. Lee TH, Chennakrishnaiah S, Audemard E, Montermini L, Meehan B, Rak J. Oncogenic ras-driven cancer cell vesiculation leads to emission of double-stranded DNA capable of interacting with target cells. Biochem Biophys Res Commun 2014;451:295-301.
155. Heitzer E, Haque IS, Roberts CES, Speicher MR. Current and future perspectives of liquid biopsies in genomics-driven oncology. Nat Rev Genet 2019;20:71-88.
156. Wan Y, Liu B, Lei H, et al. Nanoscale extracellular vesicle-derived DNA is superior to circulating cell-free DNA for mutation detection in early-stage non-small-cell lung cancer. Ann Oncol 2018;29:2379-83.
157. Castillo J, Bernard V, San Lucas FA, et al. Surfaceome profiling enables isolation of cancer-specific exosomal cargo in liquid biopsies from pancreatic cancer patients. Ann Oncol 2018;29:223-9.
158. Lázaro-Ibáñez E, Sanz-Garcia A, Visakorpi T, et al. Different gDNA content in the subpopulations of prostate cancer extracellular vesicles: apoptotic bodies, microvesicles, and exosomes. Prostate 2014;74:1379-90.
159. Krug AK, Enderle D, Karlovich C, et al. Improved EGFR mutation detection using combined exosomal RNA and circulating tumor DNA in NSCLC patient plasma. Ann Oncol 2018;29:700-6.
160. Bernard V, Kim DU, San Lucas FA, et al. Circulating nucleic acids are associated with outcomes of patients with pancreatic cancer. Gastroenterology 2019;156:108-18.e4.
161. Castellanos-Rizaldos E, Grimm DG, Tadigotla V, et al. Exosome-based detection of EGFR T790M in plasma from non-small cell lung cancer patients. Clin Cancer Res 2018;24:2944-50.
162. Wan JCM, Massie C, Garcia-Corbacho J, et al. Liquid biopsies come of age: towards implementation of circulating tumour DNA. Nat Rev Cancer 2017;17:223-38.
163. Cheng L, Hill AF. Therapeutically harnessing extracellular vesicles. Nat Rev Drug Discov 2022;21:379-99.
164. Zitvogel L, Regnault A, Lozier A, et al. Eradication of established murine tumors using a novel cell-free vaccine: dendritic cell-derived exosomes. Nat Med 1998;4:594-600.
165. Alvarez-Erviti L, Seow Y, Yin H, Betts C, Lakhal S, Wood MJ. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol 2011;29:341-5.
166. Kamerkar S, LeBleu VS, Sugimoto H, et al. Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer. Nature 2017;546:498-503.
167. Mendt M, Kamerkar S, Sugimoto H, et al. Generation and testing of clinical-grade exosomes for pancreatic cancer. JCI Insight 2018;3:99263.
168. Tian Y, Li S, Song J, et al. A doxorubicin delivery platform using engineered natural membrane vesicle exosomes for targeted tumor therapy. Biomaterials 2014;35:2383-90.
169. Usman WM, Pham TC, Kwok YY, et al. Efficient RNA drug delivery using red blood cell extracellular vesicles. Nat Commun 2018;9:2359.
170. Votteler J, Ogohara C, Yi S, et al. Designed proteins induce the formation of nanocage-containing extracellular vesicles. Nature 2016;540:292-5.
171. Wiklander OPB, Brennan MÁ, Lötvall J, Breakefield XO, El Andaloussi S. Advances in therapeutic applications of extracellular vesicles. Sci Transl Med 2019;11:eaav8521.
172. Bojmar L, Kim HS, Tobias GC, et al. Extracellular vesicle and particle isolation from human and murine cell lines, tissues, and bodily fluids. STAR Protoc 2021;2:100225.
173. Coughlan C, Bruce KD, Burgy O, et al. Exosome isolation by ultracentrifugation and precipitation and techniques for downstream analyses. Curr Protoc Cell Biol 2020;88:e110.
174. Böing AN, van der Pol E, Grootemaat AE, Coumans FA, Sturk A, Nieuwland R. Single-step isolation of extracellular vesicles by size-exclusion chromatography. J Extracell Vesicles 2014;3:23430.
175. Cheruvanky A, Zhou H, Pisitkun T, et al. Rapid isolation of urinary exosomal biomarkers using a nanomembrane ultrafiltration concentrator. Am J Physiol Renal Physiol 2007;292:F1657-61.
176. Guo SC, Tao SC, Dawn H. Microfluidics-based on-a-chip systems for isolating and analysing extracellular vesicles. J Extracell Vesicles 2018;7:1508271.
177. Im H, Shao H, Park YI, et al. Label-free detection and molecular profiling of exosomes with a nano-plasmonic sensor. Nat Biotechnol 2014;32:490-5.
178. Veerman RE, Teeuwen L, Czarnewski P, et al. Molecular evaluation of five different isolation methods for extracellular vesicles reveals different clinical applicability and subcellular origin. J Extracell Vesicles 2021;10:e12128.
179. Bordanaba-Florit G, Royo F, Kruglik SG, Falcón-Pérez JM. Using single-vesicle technologies to unravel the heterogeneity of extracellular vesicles. Nat Protoc 2021;16:3163-85.
180. Dragovic RA, Gardiner C, Brooks AS, et al. Sizing and phenotyping of cellular vesicles using nanoparticle tracking analysis. Nanomedicine 2011;7:780-8.
181. Tian Y, Ma L, Gong M, et al. Protein profiling and sizing of extracellular vesicles from colorectal cancer patients via flow cytometry. ACS Nano 2018;12:671-80.
182. Wu D, Yan J, Shen X, et al. Profiling surface proteins on individual exosomes using a proximity barcoding assay. Nat Commun 2019;10:3854.
183. Ridolfi A, Brucale M, Montis C, et al. AFM-based high-throughput nanomechanical screening of single extracellular vesicles. Anal Chem 2020;92:10274-82.
184. Chen C, Zong S, Wang Z, et al. Imaging and intracellular tracking of cancer-derived exosomes using single-molecule localization-based super-resolution microscope. ACS Appl Mater Interfaces 2016;8:25825-33.
185. Smith ZJ, Lee C, Rojalin T, et al. Single exosome study reveals subpopulations distributed among cell lines with variability related to membrane content. J Extracell Vesicles 2015;4:28533.
186. Tatischeff I, Larquet E, Falcón-Pérez JM, Turpin PY, Kruglik SG. Fast characterisation of cell-derived extracellular vesicles by nanoparticles tracking analysis, cryo-electron microscopy, and Raman tweezers microspectroscopy. J Extracell Vesicles 2012;1:19179.
187. Enciso-Martinez A, Van Der Pol E, Hau CM, et al. Label-free identification and chemical characterisation of single extracellular vesicles and lipoproteins by synchronous Rayleigh and Raman scattering. J Extracell Vesicles 2020;9:1730134.
188. Hyenne V, Ghoroghi S, Collot M, et al. Studying the fate of tumor extracellular vesicles at high spatiotemporal resolution using the zebrafish embryo. Dev Cell 2019;48:554-72.e7.
189. Verweij FJ, Revenu C, Arras G, et al. Live tracking of inter-organ communication by endogenous exosomes in vivo. Dev Cell 2019;48:573-89.e4.
190. Verweij FJ, Balaj L, Boulanger CM, et al. The power of imaging to understand extracellular vesicle biology in vivo. Nat Methods 2021;18:1013-26.
