Cancer tills the premetastatic field: Mechanistic basis and clinical implications

Clinical Cancer Research

Volumn 22, Issue 15, 2016, Pages 3725-3733

  Chin, Andrew R ^a   Wang, Shizhen Emily ^a,b  

^a CITY OF HOPE NATIONAL MEDICAL CENTER   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANGIOGENIC PROTEIN; BIOLOGICAL MARKER; CD81 ANTIGEN; CHEMOKINE RECEPTOR CXCR2; GLYPICAN 1; GRANULOCYTE COLONY STIMULATING FACTOR; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; HEAT SHOCK PROTEIN 70; HEAT SHOCK PROTEIN 72; HEAT SHOCK PROTEIN 90; MESSENGER RNA; MICRORNA; MICRORNA 100; MICRORNA 105; MICRORNA 122; MICRORNA 181C; MICRORNA 200; MICRORNA 21; MICRORNA 29A; MICRORNA 9; MONOCYTE CHEMOTACTIC PROTEIN 1; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; SCATTER FACTOR RECEPTOR; STROMAL CELL DERIVED FACTOR 1; TRANSFORMING GROWTH FACTOR BETA; TUMOR MARKER; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; VASCULOTROPIN A; VERY LATE ACTIVATION ANTIGEN 4;

BONE MARROW CELL; CANCER PROGNOSIS; CD8+ T LYMPHOCYTE; CELL HETEROGENEITY; CIRCULATING TUMOR CELL; ENDOTHELIUM CELL; EXOSOME; EXTRACELLULAR MATRIX; HUMAN; IMMUNOCOMPETENT CELL; MACROPHAGE; METABOLIC STRESS; METASTASIS; MONOCYTE; NONHUMAN; NUCLEAR REPROGRAMMING; PREMETASTATIC NICHE; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN EXPRESSION; REVIEW; STROMA CELL; TUMOR MICROENVIRONMENT; TUMOR VASCULARIZATION; ANIMAL; CYTOLOGY; IMMUNE SYSTEM; IMMUNOLOGY; METABOLISM; NEOPLASM; PATHOLOGY;

ANIMALS; BIOMARKERS; EXTRACELLULAR MATRIX; HUMANS; IMMUNE SYSTEM; NEOPLASM METASTASIS; NEOPLASMS; STROMAL CELLS; TUMOR MICROENVIRONMENT;

EID: 84980010049     PISSN: 10780432     EISSN: 15573265     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-16-0028     Document Type: Review

References (98)

1. Kaplan RN, Riba RD, Zacharoulis S, Bramley AH, Vincent L, Costa C, et al. VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature 2005;438:820-7.
2. Kaplan RN, Rafii S, Lyden D. Preparing the "soil": the premetastatic niche. Cancer Res 2006;66:11089-93.
3. Valastyan S, Weinberg RA. Tumor metastasis: molecular insights and evolving paradigms. Cell 2011;147:275-92.
4. Gupta GP, Massague J. Cancer metastasis: building a framework. Cell 2006;127:679-95.
5. Steeg PS. Tumor metastasis: mechanistic insights and clinical challenges. Nat Med 2006;12:895-904.
6. Sethi N, Kang Y. Unravelling the complexity of metastasis - molecular understanding and targeted therapies. Nat Rev Cancer 2011;11:735-48.
7. Chambers AF, Groom AC, MacDonald IC. Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer 2002;2:563-72.
8. 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.
9. Psaila B, Lyden D. The metastatic niche: adapting the foreign soil. Nat Rev Cancer 2009;9:285-93.
10. Peinado H, Lavotshkin S, Lyden D. The secreted factors responsible for premetastatic niche formation: old sayings and new thoughts. Semin Cancer Biol 2011;21:139-46.
11. Paget S. The distribution of secondary growths in cancer of the breast. 1889. Cancer Metastasis Rev 1989;8:98-101.
12. Alix-Panabieres C, Riethdorf S, Pantel K. Circulating tumor cells and bone marrow micrometastasis. Clin Cancer Res 2008;14:5013-21.
13. Podsypanina K, Du YC, Jechlinger M, Beverly LJ, Hambardzumyan D, Varmus H. Seeding and propagation of untransformed mouse mammary cells in the lung. Science 2008;321:1841-4.
14. Erler JT, Bennewith KL, Cox TR, Lang G, Bird D, Koong A, et al. Hypoxiainduced lysyl oxidase is a critical mediator of bone marrow cell recruitment to form the premetastatic niche. Cancer Cell 2009;15:35-44.
15. Hiratsuka S, Ishibashi S, Tomita T, Watanabe A, Akashi-Takamura S, Murakami M, et al. Primary tumours modulate innate immune signalling to create pre-metastatic vascular hyperpermeability foci. Nat Commun 2013;4:1853.
16. Hiratsuka S, Goel S, Kamoun WS, Maru Y, Fukumura D, Duda DG, et al. Endothelial focal adhesion kinase mediates cancer cell homing to discrete regions of the lungs via E-selectin up-regulation. Proc Natl Acad Sci U S A 2011;108:3725-30.
17. Hiratsuka S, Watanabe A, Aburatani H, Maru Y. Tumour-mediated upregulation of chemoattractants and recruitment of myeloid cells predetermines lung metastasis. Nat Cell Biol 2006;8:1369-75.
18. Hiratsuka S, Watanabe A, Sakurai Y, Akashi-Takamura S, Ishibashi S, Miyake K, et al. The S100A8-serum amyloid A3-TLR4 paracrine cascade establishes a pre-metastatic phase. Nat Cell Biol 2008;10: 1349-55.
19. Fong MY, Zhou W, Liu L, Alontaga AY, Chandra M, Ashby J, et al. Breastcancer-secreted miR-122 reprograms glucose metabolism in premetastatic niche to promote metastasis. Nat Cell Biol 2015;17:183-94.
20. Zhou W, Fong MY, Min Y, Somlo G, Liu L, Palomares MR, et al. Cancersecreted miR-105 destroys vascular endothelial barriers to promote metastasis. Cancer Cell 2014;25:501-15.
21. Kim MY, Oskarsson T, Acharyya S, Nguyen DX, Zhang XH, Norton L, et al. Tumor self-seeding by circulating cancer cells. Cell 2009;139:1315-26.
22. Chen Y, Gou X, Kong DK, Wang X, Wang J, Chen Z, et al. EMMPRIN regulates tumor growth and metastasis by recruiting bone marrow-derived cells through paracrine signaling of SDF-1 and VEGF. Oncotarget 2015;6: 32575-85.
23. Deng J, Liu Y, Lee H, Herrmann A, Zhang W, Zhang C, et al. S1PR1-STAT3 signaling is crucial for myeloid cell colonization at future metastatic sites. Cancer Cell 2012;21:642-54.
24. Sceneay J, Chow MT, Chen A, Halse HM, Wong CS, Andrews DM, et al. Primary tumor hypoxia recruits CD11b/Ly6Cmed/Ly6G immune suppressor cells and compromises NK cell cytotoxicity in the premetastatic niche. Cancer Res 2012;72:3906-11.
25. Yan HH, Jiang J, Pang Y, Achyut BR, Lizardo M, Liang X, et al. CCL9 induced by TGFbeta signaling in myeloid cells enhances tumor cell survival in the premetastatic organ. Cancer Res 2015;75:5283-98.
26. Canesin G, Cuevas EP, Santos V, Lopez-Menendez C, Moreno-Bueno G, Huang Y, et al. Lysyl oxidase-like 2 (LOXL2) and E47 EMT factor: novel partners in E-cadherin repression and early metastasis colonization. Oncogene 2015;34:951-64.
27. Wculek SK, Malanchi I. Neutrophils support lung colonization of metastasis-initiating breast cancer cells. Nature 2015;528:413-7.
28. Headley MB, Bins A, Nip A, Roberts EW, Looney MR, Gerard A, et al. Visualization of immediate immune responses to pioneer metastatic cells in the lung. Nature 2016;531:513-7.
29. Coffelt SB, Kersten K, Doornebal CW, Weiden J, Vrijland K, Hau CS, et al. IL-17-producing gammadelta T cells and neutrophils conspire to promote breast cancer metastasis. Nature 2015;522:345-8.
30. Chow A, Zhou W, Liu L, Fong MY, Champer J, Van Haute D, et al. Macrophage immunomodulation by breast cancer-derived exosomes requires Toll-like receptor 2-mediated activation of NF-kappaB. Sci Rep 2014;4:5750.
31. Nielsen SR, Quaranta V, Linford A, Emeagi P, Rainer C, Santos A, et al. Macrophage-secreted granulin supports pancreatic cancer metastasis by inducing liver fibrosis. Nat Cell Biol 2016;18:549-60.
32. Rohan TE, Xue X, Lin HM, D'Alfonso TM, Ginter PS, Oktay MH, et al. Tumor microenvironment of metastasis and risk of distant metastasis of breast cancer. J Natl Cancer Inst 2014;106:pii:dju136.
33. Ogawa F, Amano H, Eshima K, Ito Y, Matsui Y, Hosono K, et al. Prostanoid induces premetastatic niche in regional lymph nodes. J Clin Invest 2014;124:4882-94.
34. Hanna RN, Cekic C, Sag D, Tacke R, Thomas GD, Nowyhed H, et al. Patrolling monocytes control tumor metastasis to the lung. Science 2015; 350:985-90.
35. Labelle M, Begum S, Hynes RO. Platelets guide the formation of early metastatic niches. Proc Natl Acad Sci U S A 2014;111:E3053-61.
36. ZhangW,ZhangC,LiW,DengJ,HerrmannA,PricemanSJ,etal.CD8 T-cell immunosurveillance constrains lymphoid premetastatic myeloid cell accumulation. Eur J Immunol 2015;45:71-81.
37. Vadrevu SK, Chintala NK, Sharma SK, Sharma P, Cleveland C, Riediger L, et al. Complement c5a receptor facilitates cancer metastasis by altering T-cell responses in the metastatic niche. Cancer Res 2014;74:3454-65.
38. Sharma SK, Chintala NK, Vadrevu SK, Patel J, Karbowniczek M, Markiewski MM. Pulmonary alveolar macrophages contribute to the premetastatic niche by suppressing antitumor T cell responses in the lungs. J Immunol 2015;194:5529-38.
39. Grum-Schwensen B, Klingelhofer J, Beck M, Bonefeld CM, Hamerlik P, Guldberg P, et al. S100A4-neutralizing antibody suppresses spontaneous tumor progression, pre-metastatic niche formation and alters T-cell polarization balance. BMC Cancer 2015;15:44.
40. Qi F, He T, Jia L, Song N, Guo L, Ma X, et al. The miR-30 family inhibits pulmonary vascular hyperpermeability in the premetastatic phase by direct targeting of Skp2. Clin Cancer Res 2015;21:3071-80.
41. Cox TR, Bird D, Baker AM, Barker HE, Ho MW, Lang G, et al. LOX-mediated collagen crosslinking is responsible for fibrosis-enhanced metastasis. Cancer Res 2013;73:1721-32.
42. Luo X, Fu Y, Loza AJ, Murali B, Leahy KM, Ruhland MK, et al. Stromalinitiated changes in the bone promote metastatic niche development. Cell Rep 2016;14:82-92.
43. van Deventer HW, Palmieri DA, Wu QP, McCook EC, Serody JS. Circulating fibrocytes prepare the lung for cancer metastasis by recruiting Ly-6C monocytes via CCL2. J Immunol 2013;190:4861-7.
44. Duda DG, Duyverman AM, Kohno M, Snuderl M, Steller EJ, Fukumura D, et al. Malignant cells facilitate lung metastasis by bringing their own soil. Proc Natl Acad Sci U S A 2010;107:21677-82.
45. Costa-Silva B, Aiello NM, Ocean AJ, Singh S, Zhang H, Thakur BK, et al. Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver. Nat Cell Biol 2015;17:816-26.
46. Lu P, Weaver VM, Werb Z. The extracellular matrix: a dynamic niche in cancer progression. J Cell Biol 2012;196:395-406.
47. Tominaga N, Kosaka N, Ono M, Katsuda T, Yoshioka Y, Tamura K, et al. Brain metastatic cancer cells release microRNA-181c-containing extracellular vesicles capable of destructing blood-brain barrier. Nat Commun 2015;6:6716.
48. Huang Y, Song N, Ding Y, Yuan S, Li X, Cai H, et al. Pulmonary vascular destabilization in the premetastatic phase facilitates lung metastasis. Cancer Res 2009;69:7529-37.
49. Avraham HK, Jiang S, Fu Y, Nakshatri H, Ovadia H, Avraham S. Angiopoietin-2 mediates blood-brain barrier impairment and colonization of triple-negative breast cancer cells in brain. J Pathol 2014; 232:369-81.
50. Liu S, Jiang M, Zhao Q, Li S, Peng Y, Zhang P, et al. Vascular endothelial growth factor plays a critical role in the formation of the pre-metastatic niche via prostaglandin E2. Oncol Rep 2014;32:2477-84.
51. Martinez LM, Vallone VB, Labovsky V, Choi H, Hofer EL, Feldman L, et al. Changes in the peripheral blood and bone marrow from untreated advanced breast cancer patients that are associated with the establishment of bone metastases. Clin Exp Metastasis 2014;31:213-32.
52. Pal SK, Vuong W, Zhang W, Deng J, Liu X, Carmichael C, et al. Clinical and translational assessment of VEGFR1 as a mediator of the premetastatic niche in high-risk localized prostate cancer. Mol Cancer Ther 2015;14: 2896-900.
53. Garnier D, Magnus N, Lee TH, Bentley V, Meehan B, Milsom C, et al. Cancer cells induced to express mesenchymal phenotype release exosome-like extracellular vesicles carrying tissue factor. J Biol Chem 2012; 287:43565-72.
54. Gopal SK, Greening DW, Hanssen EG, Zhu HJ, Simpson RJ, Mathias RA. Oncogenic epithelial cell-derived exosomes containing Rac1 and PAK2 induce angiogenesis in recipient endothelial cells. Oncotarget. 2016 Feb 22. [Epub ahead of print].
55. Tauro BJ, Mathias RA, Greening DW, Gopal SK, Ji H, Kapp EA, et al. Oncogenic H-ras reprograms Madin-Darby canine kidney (MDCK) cellderived exosomal proteins following epithelial-mesenchymal transition. Mol Cell Proteomics 2013;12:2148-59.
56. Pasquier J, Thawadi HA, Ghiabi P, Abu-Kaoud N, Maleki M, Guerrouahen BS, et al. Microparticles mediated cross-talk between tumoral and endothelial cells promote the constitution of a pro-metastatic vascular niche through Arf6 up regulation. Cancer Microenviron 2014;7:41-59.
57. Lee E, Fertig EJ, Jin K, Sukumar S, Pandey NB, Popel AS. Breast cancer cells condition lymphatic endothelial cells within pre-metastatic niches to promote metastasis. Nat Commun 2014;5:4715.
58. Lee E, Pandey NB, Popel AS. Pre-treatment of mice with tumor-conditioned media accelerates metastasis to lymph nodes and lungs: a new spontaneous breast cancer metastasis model. Clin Exp Metastasis 2014;31:67-79.
59. Loo JM, Scherl A, Nguyen A, Man FY, Weinberg E, Zeng Z, et al. Extracellular metabolic energetics can promote cancer progression. Cell 2015;160:393-406.
60. Cox TR, Rumney RM, Schoof EM, Perryman L, Hoye AM, Agrawal A, et al. The hypoxic cancer secretome induces pre-metastatic bone lesions through lysyl oxidase. Nature 2015;522:106-10.
61. Wong CC, Tse AP, Huang YP, Zhu YT, Chiu DK, Lai RK, et al. Lysyl oxidaselike 2 is critical to tumor microenvironment and metastatic niche formation in hepatocellular carcinoma. Hepatology 2014;60:1645-58.
62. Chafe SC, Lou Y, Sceneay J, Vallejo M, Hamilton MJ, McDonald PC, et al. Carbonic anhydrase IX promotes myeloid-derived suppressor cell mobilization and establishment of a metastatic niche by stimulating G-CSF production. Cancer Res 2015;75:996-1008.
63. Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ, Lotvall JO. Exosomemediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 2007;9:654-9.
64. Skog J, Wurdinger T, van Rijn S, Meijer DH, Gainche L, Sena-Esteves M, et al. Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol 2008;10:1470-6.
65. Thery C, Zitvogel L, Amigorena S. Exosomes: composition, biogenesis and function. Nat Rev Immunol 2002;2:569-79.
66. Redzic JS, Balaj L, van der Vos KE, Breakefield XO. Extracellular RNA mediates and marks cancer progression. Semin Cancer Biol 2014;28: 14-23.
67. Melo SA, Luecke LB, Kahlert C, Fernandez AF, Gammon ST, Kaye J, et al. Glypican-1 identifies cancer exosomes and detects early pancreatic cancer. Nature 2015;523:177-82.
68. Taylor DD, Gercel-Taylor C. MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. Gynecol Oncol 2008; 110:13-21.
69. Duijvesz D, Luider T, Bangma CH, Jenster G. Exosomes as biomarker treasure chests for prostate cancer. Eur Urol 2011;59:823-31.
70. Ogata-Kawata H, Izumiya M, Kurioka D, Honma Y, Yamada Y, Furuta K, et al. Circulating exosomal microRNAs as biomarkers of colon cancer. PLoS One 2014;9:e92921.
71. 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. doi: 10.3402/jev.v3.23743.
72. Purushothaman A, Bandari SK, Liu J, Mobley JA, Brown EE, Sanderson RD. Fibronectin on the surface of myeloma cell-derived exosomes mediates exosome-cell interactions. J Biol Chem 2016;291:1652-63.
73. Sung BH, Ketova T, Hoshino D, Zijlstra A, Weaver AM. Directional cell movement through tissues is controlled by exosome secretion. Nat Commun 2015;6:7164.
74. Thuma F, Zoller M. Outsmart tumor exosomes to steal the cancer initiating cell its niche. Semin Cancer Biol 2014;28:39-50.
75. Roma-Rodrigues C, Fernandes AR, Baptista PV. Exosome in tumour microenvironment: overview of the crosstalk between normal and cancer cells. Biomed Res Int 2014;2014:179486.
76. Aleckovic M, Kang Y. Regulation of cancer metastasis by cell-free miRNAs. Biochim Biophys Acta 2015;1855:24-42.
77. Pucci F, Garris C, Lai CP, Newton A, Pfirschke C, Engblom C, et al. SCS macrophages suppress melanoma by restricting tumor-derived vesicle-B cell interactions. Science 2016;352:242-6.
78. Luga V, Zhang L, Viloria-Petit AM, Ogunjimi AA, Inanlou MR, Chiu E, et al. Exosomes mediate stromal mobilization of autocrine Wnt-PCP signaling in breast cancer cell migration. Cell 2012;151:1542-56.
79. Zhang L, Zhang S, Yao J, Lowery FJ, Zhang Q, Huang WC, et al. Microenvironment-induced PTEN loss by exosomal microRNA primes brain metastasis outgrowth. Nature 2015;527:100-4.
80. Hoshino A, Costa-Silva B, Shen TL, Rodrigues G, Hashimoto A, Tesic Mark M, et al. Tumour exosome integrins determine organotropic metastasis. Nature 2015;527:329-35.
81. Wu X, Somlo G, Yu Y, Palomares MR, Li AX, Zhou W, et al. De novo sequencing of circulating miRNAs identifies novel markers predicting clinical outcome of locally advanced breast cancer. J Transl Med 2012;10:42.
82. Peinado H, Aleckovic M, Lavotshkin S, MateiI, Costa-Silva B, Moreno-Bueno G, et al. Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nat Med 2012;18:883-91.
83. Sun D, Zhuang X, Zhang S, Deng ZB, Grizzle W, Miller D, et al. Exosomes are endogenous nanoparticles that can deliver biological information between cells. Adv Drug Deliv Rev 2013;65:342-7.
84. Maeda H. Toward a full understanding of the EPR effect in primary and metastatic tumors as well as issues related to its heterogeneity. Adv Drug Deliv Rev 2015;91:3-6.
85. Monk BJ, Poveda A, Vergote I, Raspagliesi F, Fujiwara K, Bae DS, et al. Anti-angiopoietin therapy with trebananib for recurrent ovarian cancer (TRINOVA-1): a randomised, multicentre, double-blind, placebo-controlled phase 3 trial. Lancet Oncol 2014;15:799-808.
86. Dieras V, Wildiers H, Jassem J, Dirix LY, Guastalla JP, Bono P, et al. Trebananib (AMG 386) plus weekly paclitaxel with or without bevacizumab as first-line therapy for HER2-negative locally recurrent or metastatic breast cancer: a phase 2 randomized study. Breast 2015;24: 182-90.
87. Peeters M, Strickland AH, Lichinitser M, Suresh AV, Manikhas G, Shapiro J, et al. A randomised, double-blind, placebo-controlled phase 2 study of trebananib (AMG 386) in combination with FOLFIRI in patients with previously treated metastatic colorectal carcinoma. Br J Cancer 2013;108: 503-11.
88. Bonapace L, Coissieux MM, Wyckoff J, Mertz KD, Varga Z, Junt T, et al. Cessation of CCL2 inhibition accelerates breast cancer metastasis by promoting angiogenesis. Nature 2014;515:130-3.
89. Zhuang G, Wu X, Jiang Z, Kasman I, Yao J, Guan Y, et al. Tumour-secreted miR-9 promotes endothelial cell migration and angiogenesis by activating the JAK-STAT pathway. EMBO J 2012;31:3513-23.
90. Bretz NP, Ridinger J, Rupp AK, Rimbach K, Keller S, Rupp C, et al. Body fluid exosomes promote secretion of inflammatory cytokines in monocytic cells via Toll-like receptor signaling. J Biol Chem 2013; 288:36691-702.
91. Fabbri M, Paone A, Calore F, Galli R, Gaudio E, Santhanam R, et al. MicroRNAs bind to Toll-like receptors to induce prometastatic inflammatory response. Proc Natl Acad Sci U S A 2012;109:E2110-6.
92. Hood JL, San RS, Wickline SA. Exosomes released by melanoma cells prepare sentinel lymph nodes for tumor metastasis. Cancer Res 2011;71: 3792-801.
93. Chalmin F, Ladoire S, Mignot G, Vincent J, Bruchard M, Remy-Martin JP, 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.
94. He WA, Calore F, Londhe P, Canella A, Guttridge DC, Croce CM. Microvesicles containing miRNAs promote muscle cell death in cancer cachexia via TLR7. Proc Natl Acad Sci U S A 2014;111:4525-9.
95. Webber J, Steadman R, Mason MD, Tabi Z, Clayton A. Cancer exosomes trigger fibroblast to myofibroblast differentiation. Cancer Res 2010;70: 9621-30.
96. Sanchez CA, Andahur EI, Valenzuela R, Castellon EA, Fulla JA, Ramos CG, et al. Exosomes from bulk and stem cells from human prostate cancer have a differential microRNA content that contributes cooperatively over local and pre-metastatic niche. Oncotarget 2016;7: 3993-4008.
97. Jung T, Castellana D, Klingbeil P, Cuesta Hernandez I, Vitacolonna M, Orlicky DJ, et al. CD44v6 dependence of premetastatic niche preparation by exosomes. Neoplasia 2009;11:1093-105.
98. Le MT, Hamar P, Guo C, Basar E, Perdigao-Henriques R, Balaj L, et al. miR-200-containing extracellular vesicles promote breast cancer cell metastasis. J Clin Invest 2014;124:5109-28.