Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Molecular Cancer
Published in: Molecular Cancer 1/2019

Open Access 01-12-2019 | Metastasis | Review

Emerging roles and therapeutic value of exosomes in cancer metastasis

Authors: Miaowei Wu, Guosheng Wang, Weilei Hu, Yihan Yao, Xiao-Fang Yu

Published in: Molecular Cancer | Issue 1/2019

Login to get access

Abstract

Exosomes are cell-derived vesicles of 30 to 150 nm that contain diverse proteins, nucleic acids, and lipids. These vesicles facilitate effective intercellular communication and trigger profound environmental changes. In recent years, many studies have identified diverse roles for exosomes in tumor metastasis, a major cause of cancer-related deaths; furthermore, circulating tumor-derived exosomes can drive the initiation and progression of metastasis and determine the specific target organs affected. Fortunately, our growing understanding of exosomes and relevant modification technology have provided new ideas for potential treatment of tumor metastases. Here we review recent advances concerning the role of exosomes in metastasis, focusing on their regulatory mechanisms and therapeutic targeting in advanced cancer.
Literature
1.
2.
Paget S. The distribution of secondary growths in cancer of the breast. 1889. Cancer Metastasis Rev. 1989;8:98–101.PubMed
3.
4.
5.
Peinado H, Zhang H, Matei IR, Costa-Silva B, Hoshino A, Rodrigues G, Psaila B, Kaplan RN, Bromberg JF, Kang Y, et al. Pre-metastatic niches: organ-specific homes for metastases. Nat Rev Cancer. 2017;17:302–17.PubMedCrossRef
6.
McAllister SS, Weinberg RA. The tumour-induced systemic environment as a critical regulator of cancer progression and metastasis. Nat Cell Biol. 2014;16:717–27.PubMedPubMedCentralCrossRef
7.
Cammarota F, Laukkanen MO. Mesenchymal Stem/Stromal Cells in Stromal Evolution and Cancer Progression. Stem Cells Int. 2016;2016:4824573.PubMedCrossRef
8.
Hoshino A, Costa-Silva B, Shen TL, Rodrigues G, Hashimoto A, Tesic Mark M, Molina H, Kohsaka S, Di Giannatale A, Ceder S, et al. Tumour exosome integrins determine organotropic metastasis. Nature. 2015;527:329–35.PubMedPubMedCentralCrossRef
9.
Lobb RJ, Lima LG, Moller A. Exosomes: Key mediators of metastasis and pre-metastatic niche formation. Semin Cell Dev Biol. 2017;67:3–10.PubMedCrossRef
10.
Syn N, Wang L, Sethi G, Thiery JP, Goh BC. Exosome-Mediated Metastasis: From Epithelial-Mesenchymal Transition to Escape from Immunosurveillance. Trends Pharmacol Sci. 2016;37:606–17.PubMedCrossRef
11.
Thery C, Zitvogel L, Amigorena S. Exosomes: composition, biogenesis and function. Nat Rev Immunol. 2002;2:569–79.PubMedCrossRef
12.
Wubbolts R, Leckie RS, Veenhuizen PT, Schwarzmann G, Mobius W, Hoernschemeyer J, Slot JW, Geuze HJ, Stoorvogel W: Proteomic and biochemical analyses of human B cell-derived exosomes. Potential implications for their function and multivesicular body formation. J Biol Chem 2003, 278:10963–10972.
13.
Redis RS, Calin S, Yang Y, You MJ, Calin GA. Cell-to-cell miRNA transfer: from body homeostasis to therapy. Pharmacol Ther. 2012;136:169–74.PubMedCrossRef
14.
Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ, Lotvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol. 2007;9:654–9.PubMedCrossRef
15.
16.
Shurtleff MJ, Temoche-Diaz MM, Karfilis KV, Ri S, Schekman R. Y-box protein 1 is required to sort microRNAs into exosomes in cells and in a cell-free reaction. Elife. 2016;5.
17.
Zhou W, Fong MY, Min Y, Somlo G, Liu L, Palomares MR, Yu Y, Chow A, O'Connor ST, Chin AR, et al. Cancer-secreted miR-105 destroys vascular endothelial barriers to promote metastasis. Cancer Cell. 2014;25:501–15.PubMedPubMedCentralCrossRef
18.
Zhang L, Zhang S, Yao J, Lowery FJ, Zhang Q, Huang WC, Li P, Li M, Wang X, Zhang C, et al. Microenvironment-induced PTEN loss by exosomal microRNA primes brain metastasis outgrowth. Nature. 2015;527:100–4.PubMedPubMedCentralCrossRef
19.
Luga V, Zhang L, Viloria-Petit AM, Ogunjimi AA, Inanlou MR, Chiu E, Buchanan M, Hosein AN, Basik M, Wrana JL. Exosomes mediate stromal mobilization of autocrine Wnt-PCP signaling in breast cancer cell migration. Cell. 2012;151:1542–56.PubMedCrossRef
20.
Zoller M. Tetraspanins: push and pull in suppressing and promoting metastasis. Nat Rev Cancer. 2009;9:40–55.PubMedCrossRef
21.
Shah R, Patel T, Freedman JE. Circulating Extracellular Vesicles in Human Disease. N Engl J Med. 2018;379:2180–1.PubMed
22.
Tkach M, Thery C. Communication by Extracellular Vesicles: Where We Are and Where We Need to Go. Cell. 2016;164:1226–32.PubMedCrossRef
23.
Zomer A, Maynard C, Verweij FJ, Kamermans A, Schafer R, Beerling E, Schiffelers RM, de Wit E, Berenguer J, Ellenbroek SIJ, et al. In Vivo imaging reveals extracellular vesicle-mediated phenocopying of metastatic behavior. Cell. 2015;161:1046–57.PubMedPubMedCentralCrossRef
24.
Weidle UH, Birzele F, Kollmorgen G, Ruger R. The Multiple Roles of Exosomes in Metastasis. Cancer Genomics Proteomics. 2017;14:1–15.PubMedCrossRef
25.
Steinbichler TB, Dudas J, Riechelmann H. Skvortsova, II: The role of exosomes in cancer metastasis. Semin Cancer Biol. 2017;44:170–81.PubMedCrossRef
26.
Kaplan RN, Riba RD, Zacharoulis S, Bramley AH, Vincent L, Costa C, MacDonald DD, Jin DK, Shido K, Kerns SA, et al. VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature. 2005;438:820–7.PubMedPubMedCentralCrossRef
27.
Ye X, Brabletz T, Kang Y, Longmore GD, Nieto MA, Stanger BZ, Yang J, Weinberg RA. Upholding a role for EMT in breast cancer metastasis. Nature. 2017;547:E1–3.PubMedPubMedCentralCrossRef
28.
29.
McAtee CO, Booth C, Elowsky C, Zhao L, Payne J, Fangman T, Caplan S, Henry MD, Simpson MA. Prostate tumor cell exosomes containing hyaluronidase Hyal1 stimulate prostate stromal cell motility by engagement of FAK-mediated integrin signaling. Matrix Biol. 2018.
30.
Chen L, Guo P, He Y, Chen Z, Chen L, Luo Y, Qi L, Liu Y, Wu Q, Cui Y, et al. HCC-derived exosomes elicit HCC progression and recurrence by epithelial-mesenchymal transition through MAPK/ERK signalling pathway. Cell Death Dis. 2018;9:513.PubMedPubMedCentralCrossRef
31.
Li L, Li C, Wang S, Wang Z, Jiang J, Wang W, Li X, Chen J, Liu K, Li C, Zhu G. Exosomes Derived from Hypoxic Oral Squamous Cell Carcinoma Cells Deliver miR-21 to Normoxic Cells to Elicit a Prometastatic Phenotype. Cancer Res. 2016;76:1770–80.PubMedCrossRef
32.
Shan Y, You B, Shi S, Shi W, Zhang Z, Zhang Q, Gu M, Chen J, Bao L, Liu D, You Y. Hypoxia-Induced Matrix Metalloproteinase-13 Expression in Exosomes from Nasopharyngeal Carcinoma Enhances Metastases. Cell Death Dis. 2018;9:382.PubMedPubMedCentralCrossRef
33.
Steenbeek SC, Pham TV, de Ligt J, Zomer A, Knol JC, Piersma SR, Schelfhorst T, Huisjes R, Schiffelers RM, Cuppen E, et al. Cancer cells copy migratory behavior and exchange signaling networks via extracellular vesicles. Embo j. 2018;37.
34.
Kosaka N, Iguchi H, Hagiwara K, Yoshioka Y, Takeshita F, Ochiya T. Neutral sphingomyelinase 2 (nSMase2)-dependent exosomal transfer of angiogenic microRNAs regulate cancer cell metastasis. J Biol Chem. 2013;288:10849–59.PubMedPubMedCentralCrossRef
35.
Bao L, You B, Shi S, Shan Y, Zhang Q, Yue H, Zhang J, Zhang W, Shi Y, Liu Y, et al. Metastasis-associated miR-23a from nasopharyngeal carcinoma-derived exosomes mediates angiogenesis by repressing a novel target gene TSGA10. Oncogene. 2018;37:2873–89.PubMedPubMedCentralCrossRef
36.
Fang JH, Zhang ZJ, Shang LR, Luo YW, Lin YF, Yuan Y, Zhuang SM. Hepatoma cell-secreted exosomal microRNA-103 increases vascular permeability and promotes metastasis by targeting junction proteins. Hepatology. 2018;68:1459–75.PubMedCrossRef
37.
Peinado H, Aleckovic M, Lavotshkin S, Matei I, Costa-Silva B, Moreno-Bueno G, Hergueta-Redondo M, Williams C, Garcia-Santos G, Ghajar C, et al. Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nat Med. 2012;18:883–91.PubMedPubMedCentralCrossRef
38.
Robado de Lope L, Alcibar OL, Amor Lopez A, Hergueta-Redondo M, Peinado H: Tumour-adipose tissue crosstalk: fuelling tumour metastasis by extracellular vesicles. Philos Trans R Soc Lond B Biol Sci 2018, 373.
39.
Chalmin F, Ladoire S, Mignot G, Vincent J, Bruchard M, Remy-Martin JP, Boireau W, Rouleau A, Simon B, Lanneau D, et al. Membrane-associated Hsp72 from tumor-derived exosomes mediates STAT3-dependent immunosuppressive function of mouse and human myeloid-derived suppressor cells. J Clin Invest. 2010;120:457–71.PubMedPubMedCentral
40.
Rong L, Li R, Li S, Luo R. Immunosuppression of breast cancer cells mediated by transforming growth factor-beta in exosomes from cancer cells. Oncol Lett. 2016;11:500–4.PubMedCrossRef
41.
Abusamra AJ, Zhong Z, Zheng X, Li M, Ichim TE, Chin JL, Min WP. Tumor exosomes expressing Fas ligand mediate CD8+ T-cell apoptosis. Blood Cells Mol Dis. 2005;35:169–73.CrossRefPubMed
42.
43.
Xie Y, Zhang H, Li W, Deng Y, Munegowda MA, Chibbar R, Qureshi M, Xiang J. Dendritic cells recruit T cell exosomes via exosomal LFA-1 leading to inhibition of CD8+ CTL responses through downregulation of peptide/MHC class I and Fas ligand-mediated cytotoxicity. J Immunol. 2010;185:5268–78.PubMedCrossRef
44.
Cai Z, Yang F, Yu L, Yu Z, Jiang L, Wang Q, Yang Y, Wang L, Cao X, Wang J. Activated T cell exosomes promote tumor invasion via Fas signaling pathway. J Immunol. 2012;188:5954–61.PubMedCrossRef
45.
Andreola G, Rivoltini L, Castelli C, Huber V, Perego P, Deho P, Squarcina P, Accornero P, Lozupone F, Lugini L, et al. Induction of lymphocyte apoptosis by tumor cell secretion of FasL-bearing microvesicles. J Exp Med. 2002;195:1303–16.PubMedPubMedCentralCrossRef
46.
Liu C, Yu S, Zinn K, Wang J, Zhang L, Jia Y, Kappes JC, Barnes S, Kimberly RP, Grizzle WE, Zhang HG. Murine mammary carcinoma exosomes promote tumor growth by suppression of NK cell function. J Immunol. 2006;176:1375–85.CrossRefPubMed
47.
Zhang HG, Kim H, Liu C, Yu S, Wang J, Grizzle WE, Kimberly RP, Barnes S. Curcumin reverses breast tumor exosomes mediated immune suppression of NK cell tumor cytotoxicity. Biochim Biophys Acta. 1773;2007:1116–23.
48.
Berchem G, Noman MZ, Bosseler M, Paggetti J, Baconnais S, Le Cam E, Nanbakhsh A, Moussay E, Mami-Chouaib F, Janji B, Chouaib S. Hypoxic tumor-derived microvesicles negatively regulate NK cell function by a mechanism involving TGF-beta and miR23a transfer. Oncoimmunology. 2016;5:e1062968.PubMedCrossRef
49.
Shao Y, Chen T, Zheng X, Yang S, Xu K, Chen X, Xu F, Wang L, Shen Y, Wang T, et al. Colorectal cancer-derived small extracellular vesicles establish an inflammatory premetastatic niche in liver metastasis. Carcinogenesis. 2018;39:1368–79.PubMedCrossRef
50.
Liu Y, Gu Y, Han Y, Zhang Q, Jiang Z, Zhang X, Huang B, Xu X, Zheng J, Cao X. Tumor Exosomal RNAs Promote Lung Pre-metastatic Niche Formation by Activating Alveolar Epithelial TLR3 to Recruit Neutrophils. Cancer Cell. 2016;30:243–56.PubMedCrossRef
51.
Antonopoulos D, Balatsos NAA, Gourgoulianis KI. Cancer's smart bombs: tumor-derived exosomes target lung epithelial cells triggering pre-metastatic niche formation. J Thorac Dis. 2017;9:969–72.PubMedPubMedCentralCrossRef
52.
Fang T, Lv H, Lv G, Li T, Wang C, Han Q, Yu L, Su B, Guo L, Huang S, et al. Tumor-derived exosomal miR-1247-3p induces cancer-associated fibroblast activation to foster lung metastasis of liver cancer. Nat Commun. 2018;9:191.PubMedPubMedCentralCrossRef
53.
Naito Y, Yoshioka Y, Yamamoto Y, Ochiya T. How cancer cells dictate their microenvironment: present roles of extracellular vesicles. Cell Mol Life Sci. 2017;74:697–713.PubMedCrossRef
54.
Dorayappan KDP, Wanner R, Wallbillich JJ, Saini U, Zingarelli R, Suarez AA, Cohn DE, Selvendiran K. Hypoxia-induced exosomes contribute to a more aggressive and chemoresistant ovarian cancer phenotype: a novel mechanism linking STAT3/Rab proteins. Oncogene. 2018;37:3806–21.PubMedPubMedCentralCrossRef
55.
Wang X, Luo G, Zhang K, Cao J, Huang C, Jiang T, Liu B, Su L, Qiu Z. Hypoxic Tumor-Derived Exosomal miR-301a Mediates M2 Macrophage Polarization via PTEN/PI3Kgamma to Promote Pancreatic Cancer Metastasis. Cancer Res. 2018;78:4586–98.CrossRefPubMed
56.
Lan J, Sun L, Xu F, Liu L, Hu F, Song D, Hou Z, Wu W, Luo X, Wang J, et al. M2 macrophage-derived exosomes promote cell migration and invasion in colon cancer. Cancer Res. 2018;79(1):146–58.PubMedCrossRef
57.
Zheng P, Luo Q, Wang W, Li J, Wang T, Wang P, Chen L, Zhang P, Chen H, Liu Y, et al. Tumor-associated macrophages-derived exosomes promote the migration of gastric cancer cells by transfer of functional Apolipoprotein E. Cell Death Dis. 2018;9:434.PubMedPubMedCentralCrossRef
58.
Payen VL, Porporato PE, Baselet B, Sonveaux P. Metabolic changes associated with tumor metastasis, part 1: tumor pH, glycolysis and the pentose phosphate pathway. Cell Mol Life Sci. 2016;73:1333–48.PubMedCrossRef
59.
Caneba CA, Bellance N, Yang L, Pabst L, Nagrath D. Pyruvate uptake is increased in highly invasive ovarian cancer cells under anoikis conditions for anaplerosis, mitochondrial function, and migration. Am J Physiol Endocrinol Metab. 2012;303:E1036–52.PubMedCrossRef
60.
Nomura DK, Long JZ, Niessen S, Hoover HS, Ng SW, Cravatt BF. Monoacylglycerol lipase regulates a fatty acid network that promotes cancer pathogenesis. Cell. 2010;140:49–61.PubMedPubMedCentralCrossRef
61.
Yang L, Moss T, Mangala LS, Marini J, Zhao H, Wahlig S, Armaiz-Pena G, Jiang D, Achreja A, Win J, et al. Metabolic shifts toward glutamine regulate tumor growth, invasion and bioenergetics in ovarian cancer. Mol Syst Biol. 2014;10:728.PubMedPubMedCentralCrossRef
62.
Zhao H, Yang L, Baddour J, Achreja A, Bernard V, Moss T, Marini JC, Tudawe T, Seviour EG, San Lucas FA, et al. Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism. Elife. 2016;5:e10250.PubMedPubMedCentralCrossRef
63.
Chau BN, Xin C, Hartner J, Ren S, Castano AP, Linn G, Li J, Tran PT, Kaimal V, Huang X, et al. MicroRNA-21 promotes fibrosis of the kidney by silencing metabolic pathways. Sci Transl Med. 2012;4:121ra118.CrossRef
64.
Zhu H, Shyh-Chang N, Segre AV, Shinoda G, Shah SP, Einhorn WS, Takeuchi A, Engreitz JM, Hagan JP, Kharas MG, et al. The Lin28/let-7 axis regulates glucose metabolism. Cell. 2011;147:81–94.PubMedPubMedCentralCrossRef
65.
Grange C, Tapparo M, Collino F, Vitillo L, Damasco C, Deregibus MC, Tetta C, Bussolati B, Camussi G. Microvesicles released from human renal cancer stem cells stimulate angiogenesis and formation of lung premetastatic niche. Cancer Res. 2011;71:5346–56.CrossRefPubMed
66.
Fong MY, Zhou W, Liu L, Alontaga AY, Chandra M, Ashby J, Chow A, O'Connor ST, Li S, Chin AR, et al. Breast-cancer-secreted miR-122 reprograms glucose metabolism in premetastatic niche to promote metastasis. Nat Cell Biol. 2015;17:183–94.PubMedPubMedCentralCrossRef
67.
Zhang Y, Huang S, Li P, Chen Q, Li Y, Zhou Y, Wang L, Kang M, Zhang B, Yang B, et al. Pancreatic cancer-derived exosomes suppress the production of GIP and GLP-1 from STC-1cells in vitro by down-regulating the PCSK1/3. Cancer Lett. 2018;431:190–200.PubMedCrossRef
68.
Yogev O, Henderson S, Hayes MJ, Marelli SS, Ofir-Birin Y, Regev-Rudzki N, Herrero J, Enver T. Herpesviruses shape tumour microenvironment through exosomal transfer of viral microRNAs. PLoS Pathog. 2017;13:e1006524.PubMedPubMedCentralCrossRef
69.
Hart IR, Fidler IJ. Role of organ selectivity in the determination of metastatic patterns of B16 melanoma. Cancer Res. 1980;40:2281–7.PubMed
70.
Muller A, Homey B, Soto H, Ge N, Catron D, Buchanan ME, McClanahan T, Murphy E, Yuan W, Wagner SN, et al. Involvement of chemokine receptors in breast cancer metastasis. Nature. 2001;410:50–6.PubMedCrossRef
71.
Lu X, Kang Y. Organotropism of breast cancer metastasis. J Mammary Gland Biol Neoplasia. 2007;12:153–62.PubMedCrossRef
72.
73.
Chang Q, Bournazou E, Sansone P, Berishaj M, Gao SP, Daly L, Wels J, Theilen T, Granitto S, Zhang X, et al. The IL-6/JAK/Stat3 feed-forward loop drives tumorigenesis and metastasis. Neoplasia. 2013;15:848–62.PubMedPubMedCentralCrossRef
74.
Cox TR, Rumney RMH, Schoof EM, Perryman L, Hoye AM, Agrawal A, Bird D, Latif NA, Forrest H, Evans HR, et al. The hypoxic cancer secretome induces pre-metastatic bone lesions through lysyl oxidase. Nature. 2015;522:106–10.PubMedPubMedCentralCrossRef
75.
Parolini I, Federici C, Raggi C, Lugini L, Palleschi S, De Milito A, Coscia C, Iessi E, Logozzi M, Molinari A, et al. Microenvironmental pH is a key factor for exosome traffic in tumor cells. J Biol Chem. 2009;284:34211–22.PubMedPubMedCentralCrossRef
76.
Logozzi M, Mizzoni D, Angelini DF, Di Raimo R, Falchi M, Battistini L, Fais S. Microenvironmental pH and Exosome Levels Interplay in Human Cancer Cell Lines of Different Histotypes. Cancers (Basel). 2018;10.
77.
Coffelt SB, Wellenstein MD, de Visser KE. Neutrophils in cancer: neutral no more. Nat Rev Cancer. 2016;16:431–46.PubMedCrossRef
78.
Costa-Silva B, Aiello NM, Ocean AJ, Singh S, Zhang H, Thakur BK, Becker A, Hoshino A, Mark MT, Molina H, et al. Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver. Nat Cell Biol. 2015;17:816–26.PubMedPubMedCentralCrossRef
79.
Yu Z, Zhao S, Ren L, Wang L, Chen Z, Hoffman RM, Zhou J. Pancreatic cancer-derived exosomes promote tumor metastasis and liver pre-metastatic niche formation. Oncotarget. 2017;8:63461–83.PubMedPubMedCentral
80.
Zhang H, Deng T, Liu R, Bai M, Zhou L, Wang X, Li S, Wang X, Yang H, Li J, et al. Exosome-delivered EGFR regulates liver microenvironment to promote gastric cancer liver metastasis. Nat Commun. 2017;8:15016.PubMedPubMedCentralCrossRef
81.
Valiente M, Obenauf AC, Jin X, Chen Q, Zhang XH, Lee DJ, Chaft JE, Kris MG, Huse JT, Brogi E, Massague J. Serpins promote cancer cell survival and vascular co-option in brain metastasis. Cell. 2014;156:1002–16.PubMedPubMedCentralCrossRef
82.
83.
Kodack DP, Askoxylakis V, Ferraro GB, Fukumura D, Jain RK. Emerging strategies for treating brain metastases from breast cancer. Cancer Cell. 2015;27:163–75.PubMedPubMedCentralCrossRef
84.
Xing F, Liu Y, Wu SY, Wu K, Sharma S, Mo YY, Feng J, Sanders S, Jin G, Singh R, et al. Loss of XIST in Breast Cancer Activates MSN-c-Met and Reprograms Microglia via Exosomal miRNA to Promote Brain Metastasis. Cancer Res. 2018;78:4316–30.PubMedCrossRefPubMedCentral
85.
Zhao H, Achreja A, Iessi E, Logozzi M, Mizzoni D, Di Raimo R, Nagrath D, Fais S. The key role of extracellular vesicles in the metastatic process. Biochim Biophys Acta Rev Cancer. 1869;2018:64–77.
86.
Probert C, Dottorini T, Speakman A, Hunt S, Nafee T, Fazeli A, Wood S, Brown JE, James V. Communication of prostate cancer cells with bone cells via extracellular vesicle RNA; a potential mechanism of metastasis. Oncogene. 2018. Published online October 23, 2018.
87.
Valencia K, Luis-Ravelo D, Bovy N, Anton I, Martinez-Canarias S, Zandueta C, Ormazabal C, Struman I, Tabruyn S. Rebmann V, et al: miRNA cargo within exosome-like vesicle transfer influences metastatic bone colonization. Mol Oncol. 2014;8:689–703.PubMedPubMedCentralCrossRef
88.
Hashimoto K, Ochi H, Sunamura S, Kosaka N, Mabuchi Y, Fukuda T, Yao K, Kanda H, Ae K, Okawa A, 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.PubMedPubMedCentralCrossRef
89.
Karlsson T, Lundholm M, Widmark A, Persson E. Tumor Cell-Derived Exosomes from the Prostate Cancer Cell Line TRAMP-C1 Impair Osteoclast Formation and Differentiation. PLoS One. 2016;11:e0166284.PubMedPubMedCentralCrossRef
90.
Cheshomi H, Matin MM. Exosomes and their importance in metastasis, diagnosis, and therapy of colorectal cancer. J Cell Biochem. 2018.
91.
Ramani VC, Purushothaman A, Stewart MD, Thompson CA, Vlodavsky I, Au JL, Sanderson RD. The heparanase/syndecan-1 axis in cancer: mechanisms and therapies. Febs j. 2013;280:2294–306.PubMedPubMedCentralCrossRef
92.
Baietti MF, Zhang Z, Mortier E, Melchior A, Degeest G, Geeraerts A, Ivarsson Y, Depoortere F, Coomans C, Vermeiren E, et al. Syndecan-syntenin-ALIX regulates the biogenesis of exosomes. Nat Cell Biol. 2012;14:677–85.PubMedCrossRef
93.
Thompson CA, Purushothaman A, Ramani VC, Vlodavsky I, Sanderson RD. Heparanase regulates secretion, composition, and function of tumor cell-derived exosomes. J Biol Chem. 2013;288:10093–9.PubMedPubMedCentralCrossRef
94.
Sento S, Sasabe E, Yamamoto T. Application of a Persistent Heparin Treatment Inhibits the Malignant Potential of Oral Squamous Carcinoma Cells Induced by Tumor Cell-Derived Exosomes. PLoS One. 2016;11:e0148454.PubMedPubMedCentralCrossRef
95.
Nishida-Aoki N, Tominaga N, Takeshita F, Sonoda H, Yoshioka Y, Ochiya T. Disruption of Circulating Extracellular Vesicles as a Novel Therapeutic Strategy against Cancer Metastasis. Mol Ther. 2017;25:181–91.PubMedPubMedCentralCrossRef
96.
de la Fuente A, Alonso-Alconada L, Costa C, Cueva J, Garcia-Caballero T, Lopez-Lopez R, Abal M. M-Trap: Exosome-Based Capture of Tumor Cells as a New Technology in Peritoneal Metastasis. J Natl Cancer Inst. 2015;107:djv184.
97.
Logozzi M, Angelini DF, Iessi E, Mizzoni D, Di Raimo R, Federici C, Lugini L, Borsellino G, Gentilucci A, Pierella F, et al. Increased PSA expression on prostate cancer exosomes in in vitro condition and in cancer patients. Cancer Lett. 2017;403:318–29.PubMedCrossRef
98.
Federici C, Petrucci F, Caimi S, Cesolini A, Logozzi M, Borghi M, D'Ilio S, Lugini L, Violante N, Azzarito T, et al. Exosome release and low pH belong to a framework of resistance of human melanoma cells to cisplatin. PLoS One. 2014;9:e88193.PubMedPubMedCentralCrossRef
99.
Zhang Y, Yang P, Wang XF. Microenvironmental regulation of cancer metastasis by miRNAs. Trends Cell Biol. 2014;24:153–60.PubMedCrossRef
100.
Hong BS, Cho JH, Kim H, Choi EJ, Rho S, Kim J, Kim JH, Choi DS, Kim YK, Hwang D, Gho YS. Colorectal cancer cell-derived microvesicles are enriched in cell cycle-related mRNAs that promote proliferation of endothelial cells. BMC Genomics. 2009;10:556.PubMedPubMedCentralCrossRef
101.
Clancy C, Khan S, Glynn CL, Holian E, Dockery P, Lalor P, Brown JA, Joyce MR, Kerin MJ, Dwyer RM. Screening of exosomal microRNAs from colorectal cancer cells. Cancer Biomark. 2016;17:427–35.PubMedCrossRef
102.
Zaharie F, Muresan MS, Petrushev B, Berce C, Gafencu GA, Selicean S, Jurj A, Cojocneanu-Petric R, Lisencu CI, Pop LA, et al. Exosome-Carried microRNA-375 Inhibits Cell Progression and Dissemination via Bcl-2 Blocking in Colon Cancer. J Gastrointestin Liver Dis. 2015;24:435–43.PubMed
103.
Teng Y, Ren Y, Hu X, Mu J, Samykutty A, Zhuang X, Deng Z, Kumar A, Zhang L, Merchant ML, et al. MVP-mediated exosomal sorting of miR-193a promotes colon cancer progression. Nat Commun. 2017;8:14448.PubMedPubMedCentralCrossRef
104.
Escudier B, Dorval T, Chaput N, Andre F, Caby MP, Novault S, Flament C, Leboulaire C, Borg C, Amigorena S, et al. Vaccination of metastatic melanoma patients with autologous dendritic cell (DC) derived-exosomes: results of thefirst phase I clinical trial. J Transl Med. 2005;3:10.PubMedPubMedCentralCrossRef
105.
Morse MA, Garst J, Osada T, Khan S, Hobeika A, Clay TM, Valente N, Shreeniwas R, Sutton MA, Delcayre A, et al. A phase I study of dexosome immunotherapy in patients with advanced non-small cell lung cancer. J Transl Med. 2005;3:9.PubMedPubMedCentralCrossRef
106.
Boulikas T. Clinical overview on Lipoplatin: a successful liposomal formulation of cisplatin. Expert Opin Investig Drugs. 2009;18:1197–218.PubMedCrossRef
107.
Ha D, Yang N, Nadithe V. Exosomes as therapeutic drug carriers and delivery vehicles across biological membranes: current perspectives and future challenges. Acta Pharm Sin B. 2016;6:287–96.PubMedPubMedCentralCrossRef
108.
Kim MS, Haney MJ, Zhao Y, Mahajan V, Deygen I, Klyachko NL, Inskoe E, Piroyan A, Sokolsky M, Okolie O, et al. Development of exosome-encapsulated paclitaxel to overcome MDR in cancer cells. Nanomedicine. 2016;12:655–64.PubMedCrossRef
109.
110.
Dos Anjos PB, da Luz Andres Cordero F, Socorro Faria S, Peixoto Ferreira de Souza L, Cristina Brigido Tavares P, Alonso Goulart V, Fontes W, Ricardo Goulart L, Jose Barbosa Silva M. The multifaceted role of extracellular vesicles in metastasis: Priming the soil for seeding. Int J Cancer. 2017;140:2397–407.CrossRef
111.
Tian Y, Li S, Song J, Ji T, Zhu M, Anderson GJ, Wei J, Nie G. A doxorubicin delivery platform using engineered natural membrane vesicle exosomes for targeted tumor therapy. Biomaterials. 2014;35:2383–90.PubMedCrossRef
112.
Ohno S, Takanashi M, Sudo K, Ueda S, Ishikawa A, Matsuyama N, Fujita K, Mizutani T, Ohgi T, Ochiya T, et al. Systemically injected exosomes targeted to EGFR deliver antitumor microRNA to breast cancer cells. Mol Ther. 2013;21:185–91.PubMedCrossRef
113.
Mizrak A, Bolukbasi MF, Ozdener GB, Brenner GJ, Madlener S, Erkan EP, Strobel T, Breakefield XO, Saydam O. Genetically engineered microvesicles carrying suicide mRNA/protein inhibit schwannoma tumor growth. Mol Ther. 2013;21:101–8.PubMedCrossRef
114.
Yang T, Martin P, Fogarty B, Brown A, Schurman K, Phipps R, Yin VP, Lockman P, Bai S. Exosome delivered anticancer drugs across the blood-brain barrier for brain cancer therapy in Danio rerio. Pharm Res. 2015;32:2003–14.PubMedPubMedCentralCrossRef
115.
Mathieu M, Martin-Jaular L, Lavieu G, Thery C. Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication. Nat Cell Biol. 2019;21:9–17.PubMedCrossRef
116.
Belli C, Trapani D, Viale G, D'Amico P, Duso BA, Della Vigna P, Orsi F, Curigliano G. Targeting the microenvironment in solid tumors. Cancer Treat Rev. 2018;65:22–32.PubMedCrossRef
117.
Mazzocca A, Ferraro G, Misciagna G, Fais S. Moving the systemic evolutionary approach to cancer forward: Therapeutic implications. Med Hypotheses. 2018;121:80–7.PubMedCrossRef
118.
Aleckovic M, Kang Y. Welcoming Treat: Astrocyte-Derived Exosomes Induce PTEN Suppression to Foster Brain Metastasis. Cancer Cell. 2015;28:554–6.PubMedCrossRef
119.
Achreja A, Zhao H, Yang L, Yun TH, Marini J, Nagrath D. Exo-MFA - A 13C metabolic flux analysis framework to dissect tumor microenvironment-secreted exosome contributions towards cancer cell metabolism. Metab Eng. 2017;43:156–72.PubMedCrossRefPubMedCentral
120.
Olmeda D, Cerezo-Wallis D, Riveiro-Falkenbach E, Pennacchi PC, Contreras-Alcalde M, Ibarz N, Cifdaloz M, Catena X, Calvo TG, Canon E, et al. Whole-body imaging of lymphovascular niches identifies pre-metastatic roles of midkine. Nature. 2017;546:676–80.PubMedPubMedCentralCrossRef
121.
122.
Chen C, Zong S, Wang Z, Lu J, Zhu D, Zhang Y, Cui Y. Imaging and Intracellular Tracking of Cancer-Derived Exosomes Using Single-Molecule Localization-Based Super-Resolution Microscope. ACS Appl Mater Interfaces. 2016;8:25825–33.PubMedCrossRef
123.
124.
Lim C, Broqueres-You D, Brouland JP, Merkulova-Rainon T, Faussat AM, Hilal R, Rouquie D, Eveno C, Audollent R, Levy BI, Pocard M. Hepatic ischemia-reperfusion increases circulating bone marrow-derived progenitor cells and tumor growth in a mouse model of colorectal liver metastases. J Surg Res. 2013;184:888–97.PubMedCrossRef
125.
Govaert KM, Emmink BL, Nijkamp MW, Cheung ZJ, Steller EJ, Fatrai S, de Bruijn MT, Kranenburg O, Borel Rinkes IH. Hypoxia after liver surgery imposes an aggressive cancer stem cell phenotype on residual tumor cells. Ann Surg. 2014;259:750–9.PubMedCrossRef
126.
Jiao SF, Sun K, Chen XJ, Zhao X, Cai N, Liu YJ, Xu LM, Kong XM, Wei LX. Inhibition of tumor necrosis factor alpha reduces the outgrowth of hepatic micrometastasis of colorectal tumors in a mouse model of liver ischemia-reperfusion injury. J Biomed Sci. 2014;21:1.PubMedPubMedCentralCrossRef
127.
van der Bilt JD, Kranenburg O, Nijkamp MW, Smakman N, Veenendaal LM, Te Velde EA, Voest EE, van Diest PJ, Borel Rinkes IH. Ischemia/reperfusion accelerates the outgrowth of hepatic micrometastases in a highly standardized murine model. Hepatology. 2005;42:165–75.PubMedCrossRef
128.
Nguyen DX, Bos PD, Massague J. Metastasis: from dissemination to organ-specific colonization. Nat Rev Cancer. 2009;9:274–84.PubMedCrossRef
129.
130.
Yang L, Venneti S, Nagrath D. Glutaminolysis: A Hallmark of Cancer Metabolism. Annu Rev Biomed Eng. 2017;19:163–94.PubMedCrossRef
131.
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.PubMedCrossRef
Metadata
Title
Emerging roles and therapeutic value of exosomes in cancer metastasis
Authors
Miaowei Wu
Guosheng Wang
Weilei Hu
Yihan Yao
Xiao-Fang Yu
Publication date
01-12-2019
Publisher
BioMed Central
Keyword
Metastasis
Published in
Molecular Cancer / Issue 1/2019
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/s12943-019-0964-8

Other articles of this Issue 1/2019

Molecular Cancer 1/2019 Go to the issue

Research

Lung adenocarcinoma-intrinsic GBE1 signaling inhibits anti-tumor immunity

Correction

Correction to: Circular RNA YAP1 inhibits the proliferation and invasion of gastric cancer cells by regulating the miR-367-5p/p27 Kip1 axis

Review

mRNA-to-protein translation in hypoxia

Research

Circular RNA FOXP1 promotes tumor progression and Warburg effect in gallbladder cancer by regulating PKLR expression

Research

LncRNA PVT1 up-regulation is a poor prognosticator and serves as a therapeutic target in esophageal adenocarcinoma

Review

Exosome-orchestrated hypoxic tumor microenvironment
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits