Skip to main content

Advertisement

SpringerLink
Log in

Do tumor exosome integrins alone determine organotropic metastasis?

  • Review
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Metastasis is the most life-threatening event in cancer patients, so the key strategy to treat cancer should be preventing tumor spread. Predicting the site of probable hematogenous metastasis is important for determining the therapeutic algorithm that could prevent the spread of tumor cells. Certain hopes for solving this problem appeared owing to study showing the association between specific integrins on tumor exosomes surface and the site of future metastasis. Numerous experimental data indicate the ability of exosomes to transfer various phlogogenic factors to the target organ, which can lead to the formation of inflammatory foci. Studies of T-lymphocytes homing show that expression of various adhesion molecules including ligands for integrins highly increases on the endothelium during inflammation. Such a mechanism underlies not only in leukocyte transvasation, but, apparently, in the accumulation of bone marrow precursor cells and the formation of a premetastatic niche. This review summarizes the most significant data on the role exosomes to induce inflammation, which leads to the recruiting of bone marrow precursors and the establishment of premetastatic niches.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Barcellos-Hoff MH, Lyden D, Wang TC (2013) The evolution of the cancer niche during multistage carcinogenesis. Nat Rev Cancer 13(7):511–518

    Article  CAS  PubMed  Google Scholar 

  2. Dudas J (2015) Supportive and rejective functions of tumor stroma on tumor cell growth, survival, and invasivity: the cancer evolution. Front Oncol 5:44

    Article  PubMed  PubMed Central  Google Scholar 

  3. Wan Z, Gao X, Dong Y (2018) Exosome-mediated cell-cell communication in tumor progression. Am J Cancer Res 8(9):1661–1673

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Hoshino A, Costa-Silva B, Shen TL (2015) Tumour exosome integrins determine organotropic metastasis. Nature 527(7578):329–35

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Steinbichler TB, Dudás J, Skvortsov S et al (2019) Therapy resistance mediated by exosomes. Mol Cancer 18:58

    Article  PubMed  PubMed Central  Google Scholar 

  6. Sharma A (2017) Chemoresistance in cancer cells: exosomes as potential regulators of therapeutic tumor heterogeneity. Nanomedicine 12:17

    Google Scholar 

  7. McNamee N (1870) O'Driscoll L (2018) Extracellular vesicles and anti-cancer drug resistance. Biochim Biophys Acta Rev Cancer 2:123–136

    Google Scholar 

  8. Thery C, Zitvogel L, Amigorena S (2002) Exosomes: composition, biogenesis and function. Nat Rev Immunol 2:569–579

    Article  CAS  PubMed  Google Scholar 

  9. Trams EG, Lauter CJ, Salem N, Heine U Jr (1981) Exfoliation of membrane ecto-enzymes in the form of micro-vesicles. Biochim Biophys Acta 645(1):63–70

    Article  CAS  PubMed  Google Scholar 

  10. Harding C, Heuser J, Stahl P (1984) Endocytosis and intracellular processing of transferrin and colloidal gold-transferrin in rat reticulocytes: demonstration of a pathway for receptor shedding. Eur J Cell Biol 35(2):256–63

    CAS  PubMed  Google Scholar 

  11. Pan BT, Johnstone RM (1983) Fate of the transferrin receptor during maturation of sheep reticulocytes in vitro: selective externalization of the receptor. Cell 33(3):967–78

    Article  CAS  PubMed  Google Scholar 

  12. Teo H, Perisic O, González B, Williams RL (2004) ESCRT-II, an endosome-associated complex required for protein sorting: crystal structure and interactions with ESCRT-III and membranes. Dev Cell 4:559–69

    Article  Google Scholar 

  13. Larios J, Mercier V, Roux A (2020) ALIX- and ESCRT-III-dependent sorting of tetraspanins to exosomes. J Cell Biol 219(3):e201904113

    Article  CAS  PubMed Central  Google Scholar 

  14. Hurley JH, Hanson PI (2010) Membrane budding and scission by the ESCRT machinery: it's all in the neck. Nat Rev Mol Cell Biol 11:556–566

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Wollert T, Wunder C, Lippincott-Schwartz J, Hurley JH (2009) Membrane scission by the ESCRT-III complex. Nature 458:172–177

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Stuffers S, Sem Wegner C, Stenmark H, Brech A (2009) Multivesicular endosome biogenesis in the absence of ESCRTs. Traffic 10:925–937

    Article  CAS  PubMed  Google Scholar 

  17. Haraszti RA, Didiot MC, Sapp E (2016) High-resolution proteomic and lipidomic analysis of exosomes and microvesicles from different cell sources. J Extracell Vesicles 5:32570

    Article  CAS  PubMed  Google Scholar 

  18. Lazar I, Clement E, Ducoux-Petit M (2015) Proteome characterization of melanoma exosomes reveals a specific signature for metastatic cell lines. Pigment Cell Melanoma Res 28(4):464–75

    Article  CAS  PubMed  Google Scholar 

  19. Blanchard N, Lankar D, Faure F, Regnault A, Dumont C, Raposo G et al (2002) TCR activation of human T cells induces the production of exosomes bearing the TCR/CD3/zeta complex. J Immunol 168(7):3235–3241

    Article  CAS  PubMed  Google Scholar 

  20. Takeuchi T, Suzuki M, Fujikake N (2015) Intercellular chaperone transmission via exosomes contributes to maintenance of protein homeostasis at the organismal level. Proc Natl Acad Sci USA 112(19):E2497–506

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Takeda Y et al (2007) Deletion of tetraspanin Cd151 results in decreased pathologic angiogenesis in vivo and in vitro. Blood 109:1524–1532

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Wortzel I, Dror S, Kenific CM, Lyden D (2019) Exosome-mediated metastasis: communication from a distance. Dev Cell 49(3):347–360

    Article  CAS  PubMed  Google Scholar 

  23. Bernard V, Kim DU, San Lucas FA et al (2019) Circulating nucleic acids are associated with outcomes of patients with pancreatic cancer. Gastroenterology 156:108–118

    Article  CAS  PubMed  Google Scholar 

  24. Mohrmann L, Huang HJ, Hong DS et al (2018) Liquid biopsies using plasma exosomal nucleic acids and plasma cell-free DNA compared with clinical outcomes of patients with advanced cancers. Clin Cancer Res 24:181–188

    Article  CAS  PubMed  Google Scholar 

  25. Vyas P, Balakier H, Librach CL et al (2019) Ultrastructural identification of CD9 positive extracellular vesicles released from human embryos and transported through the zona pellucida. Syst Biol Reprod Med 65(4):273–280

    Article  PubMed  Google Scholar 

  26. Wang X, Zhong W, Bu J et al (2019) Exosomal protein CD82 as a diagnostic biomarker for precision medicine for breast cancer. Mol Carcinog 58(5):674–685

    Article  CAS  PubMed  Google Scholar 

  27. Kowal J, Arras G, Colombo M et al (2016) Proteomic comparison defines novel markers to characterize heterogeneous populations of extracellular vesicle subtypes. Proc Natl Acad Sci USA 113(8):E968–77

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Lu J, Li J, Liu S et al (2017) Exosomal tetraspanins mediate cancer metastasis by altering host microenvironment. Oncotarget 8(37):62803–62815

    Article  PubMed  PubMed Central  Google Scholar 

  29. Singh A, Fedele C, Lu H (2016) Exosome-mediated transfer of αvβ3 integrin from tumorigenic to nontumorigenic cells promotes a migratory phenotype. Mol Cancer Res. 14(11):1136–1146

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Rieu S, Géminard C, Rabesandratana H et al (2000) Exosomes released during reticulocyte maturation bind to fibronectin via integrin alpha4beta1. Eur J Biochem 267(2):583–90

    Article  CAS  PubMed  Google Scholar 

  31. Lobos-González L, Bustos R, Campos A (2020) Exosomes released upon mitochondrial ASncmtRNA knockdown reduce tumorigenic properties of malignant breast cancer cells. Sci Rep 10(1):343

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Véron P, Segura E, Sugano G et al (2005) Accumulation of MFG-E8/lactadherin on exosomes from immature dendritic cells. Blood Cells Mol Dis 35(2):81–8

    Article  CAS  PubMed  Google Scholar 

  33. Lee HM, Choi EJ, Kim JH et al (2010) A membranous form of ICAM-1 on exosomes efficiently blocks leukocyte adhesion to activated endothelial cells. Biochem Biophys Res Commun 397:251–256

    Article  CAS  PubMed  Google Scholar 

  34. Tang X, Chang C, Guo J (2019) Tumour-secreted hsp90α on external surface of exosomes mediates tumour - stromal cell communication via autocrine and paracrine mechanisms. Sci Rep 9(1):15108

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Chanteloup G, Cordonnier M, Isambert N et al (2019) Membrane-bound exosomal HSP70 as a biomarker for detection and monitoring of malignant solid tumours: a pilot study. Pilot Feasibility Study 6:35

    Article  Google Scholar 

  36. Caruso Bavisotto C, Cappello F, Macario AJL et al (2017) Exosomal HSP60: a potentially useful biomarker for diagnosis, assessing prognosis, and monitoring response to treatment. Expert Rev Mol Diagn. 17(9):815–822

    Article  CAS  PubMed  Google Scholar 

  37. Batulan Z, Venu VKP, Li Y et al (2016) Extracellular release and signaling by heat shock protein 27: role in modifying vascular inflammation. Front Immunol 7:285

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Hiltbrunner S, Larssen P, Eldh M et al (2016) Exosomal cancer immunotherapy is independent of MHC molecules on exosomes. Oncotarget 7(25):38707–38717

    Article  PubMed  PubMed Central  Google Scholar 

  39. Hessvik NP, Llorente A (2018) Current knowledge on exosome biogenesis and release. Cell Mol Life Sci. 75(2):193–208

    Article  CAS  PubMed  Google Scholar 

  40. Fiandaca MS, Kapogiannis D, Mapstone M et al (2015) Identification of preclinical Alzheimer’s disease by a profile of pathogenic proteins in neurally derived blood exosomes: a case-control study. Alzheimers Dement 11(6):600–607.E601

    Article  PubMed  Google Scholar 

  41. Adamo A, Brandi J, Caligola S et al (2019) Extracellular vesicles mediate mesenchymal stromal cell-dependent regulation of B cell PI3K-AKT signaling pathway and actin cytoskeleton. Front Immunol 10:446

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Larios J, Mercier V, Roux A, Gruenberg J et al (2020) ALIX- and ESCRT-III-dependent sorting of tetraspanins to exosomes. J Cell Biol 219(3):e201904113

    Article  CAS  PubMed Central  Google Scholar 

  43. Buzás EI, Tóth EÁ, Sódar BW et al (2018) Molecular interactions at the surface of extracellular vesicles. Semin Immunopathol 40(5):453–464

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Sharma P, Diergaarde B, Ferrone S et al (2020) Melanoma cell-derived exosomes in plasma of melanoma patients suppress functions of immune effector cells. Sci Rep 10(1):92

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Rivoltini L, Chiodoni C, Squarcina P et al (2016) TNF-related apoptosis-inducing ligand (TRAIL)—armed exosomes deliver proapoptotic signals to tumor site. Clin Cancer Res 22:3499–3512

    Article  CAS  PubMed  Google Scholar 

  46. Amirrad F, Pytak PA, Sadeghiani-Pelar N (2020) Prostate field cancerization and exosomes: association between CD9, early growth response 1 and fatty acid synthase. Int J Oncol 56(4):957–968

    CAS  PubMed  Google Scholar 

  47. Jella KK, Yu L, Yue Q (2016) Exosomal GAPDH from proximal tubule cells regulate ENaC activity. PLoS On 11(11):e0165763

    Article  CAS  Google Scholar 

  48. Lugini L, Valtieri M, Federici C et al (2016) Exosomes from human colorectal cancer induce a tumor-like behavior in colonic mesenchymal stromal cells. Oncotarget 7(31):50086–50098

    Article  PubMed  PubMed Central  Google Scholar 

  49. Yi H, Zheng X, Song J et al (2015) Exosomes mediated pentose phosphate pathway in ovarian cancer metastasis: a proteomics analysis. Int J Clin Exp Pathol 8(12):15719–15728

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Zhang H-G, Liu C, Su K et al (2006) A membrane form of TNF-alpha presented by exosomes delays T cell activation-induced cell death. J Immunol 176(12):7385–93

    Article  CAS  PubMed  Google Scholar 

  51. Shelke GV, Yin Y, Jang SC et al (2019) Endosomal signalling via exosome surface TGFβ-1. J Extracell Vesicles. 8(1):1650458

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Higginbotham JN, Zhang Q, Jeppesen DK et al (2016) Identification and characterization of EGF receptor in individual exosomes by fluorescence-activated vesicle sorting. J Extracell Vesicles 5:29254

    Article  CAS  PubMed  Google Scholar 

  53. Huang X, Yuan T, Tschannen M et al (2013) Characterization of human plasma-derived exosomal RNAs by deep sequencing. BMC Genomics 14:319

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Baroni S, Romero-Cordoba S, Plantamura I (2016) Exosome-mediated delivery of miR-9 induces cancer-associated fibroblast-like properties in human breast fibroblasts. Cell Death Dis 7(7):e2312

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Shen M et al (2019) Chemotherapy-induced extracellular vesicle miRNAs promote breast cancer stemness by targeting OneCUT2. Cancer Res 79(14):3608–3621

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Ma Y et al (2019) Exosomes released from neural progenitor cells and induced neural progenitor cells regulate neurogenesis through miR-21a. Cell Commun Signal 17(1):96

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. Li S-L, An N, Liu B et al (2019) Exosomes from LNCaP cells promote osteoblast activity through miR-375 transfer. Oncol Lett 17(5):4463–4473

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Cai Q, Zhu A, Gong L (2018) Exosomes of glioma cells deliver miR-148a to promote proliferation and metastasis of glioblastoma via targeting CADM1. Bull Cancer 105(7–8):643–651

    Article  PubMed  Google Scholar 

  59. Ridder K, Keller S, Dams M et al (2014) Extracellular vesicle-mediated transfer of genetic information between the hematopoietic system and the brain in response to inflammation. PLoS Biol 12(6):e1001874

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Eirin A, Zhu XY, Puranik AS et al (2017) Integrated transcriptomic and proteomic analysis of the molecular cargo of extracellular vesicles derived from porcine adipose tissue-derived mesenchymal stem cells. PLoS One 12(3):e0174303

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. Li Q, Shao Y, Zhang X, Zheng T et al (2015) Plasma long noncoding RNA protected by exosomes as a potential stable biomarker for gastric cancer. Tumour Biol 36(3):2007–12

    Article  CAS  PubMed  Google Scholar 

  62. Pan L, Liang W, Fu M, Huang ZH, Li X, Zhang W et al (2017) Exosomes-mediated transfer of long noncoding RNA ZFAS1 promotes gastric cancer progression. J. Cancer Res Clin Oncol 143:991–1004

    Article  CAS  PubMed  Google Scholar 

  63. Thakur BK, Zhang H, Becker A et al (2014) Double-stranded DNA in exosomes: a novel biomarker in cancer detection. Cell Res 24(6):766–9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Kahlert C, Melo SA, Protopopov A et al (2014) 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 289(7):3869–75

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Phuyal S, Skotland T, Hessvik NP et al (2015) The ether lipid precursor hexadecylglycerol stimulates the release and changes the composition of exosomes derived from PC-3 cells. J Biol Chem 290:4225–4237

    Article  CAS  PubMed  Google Scholar 

  66. Skotland T, Hessvik NP, Sandvig K, Llorente A (2019) Exosomal lipid composition and the role of ether lipids and phosphoinositides in exosome biology. J Lipid Res 60(1):9–18

    Article  CAS  PubMed  Google Scholar 

  67. Sharma R, Huang X, Brekken RA (2017) Detection of phosphatidylserine-positive exosomes for the diagnosis of early-stage malignancies. Br J Cancer 117(4):545–552

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Maia J, Caja S, Strano Moraes MC, Couto N, Costa-Silva B (2018) Exosome-based cell-cell communication in the tumor microenvironment. Front Cell Dev Biol 6:18

    Article  PubMed  PubMed Central  Google Scholar 

  69. Tai YL, Chen KC, Hsieh JT, Shen TL (2018) Exosomes in cancer development and clinical applications. Cancer Sci 109(8):2364–2374

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Rajagopal C, Harikumar KB (2018) The origin and functions of exosomes in cancer. Front Oncol 8:66

    Article  PubMed  PubMed Central  Google Scholar 

  71. Raimondo S, Saieva L, Corrado C (2015) Chronic myeloid leukemia-derived exosomes promote tumor growth through an autocrine mechanism. Cell Commun Signal 13:8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Qu JL, Qu XJ, Zhao MF, Teng YE (2009) Gastric cancer exosomes promote tumour cell proliferation through PI3K/Akt and MAPK/ERK activation. Dig Liver Dis 41(12):875–80

    Article  CAS  PubMed  Google Scholar 

  73. Yang L, Wu XH, Wang D, Luo CL, Chen LX (2013) Bladder cancer cell-derived exosomes inhibit tumor cell apoptosis and induce cell proliferation in vitro. Mol Med Rep 8:1272–1278

    Article  CAS  PubMed  Google Scholar 

  74. Chen G, Huang AC, Zhang W et al (2018) Exosomal PD-L1 contributes to immunosuppression and is associated with anti-PD-1 response. Nature 560:382–386

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Aga M, Bentz GL, Raffa S, Torrisi MR, Kondo S, Wakisaka N et al (2014) Exosomal HIF1alpha supports invasive potential of nasopharyngealcarcinoma-associated LMP1-positive exosomes. Oncogene 33(37):4613–4622

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. You Y, Shan Y, Chen J, Yue H, You B, Shi S et al (2015) Matrix metalloproteinase13-containing exosomes promote nasopharyngeal carcinoma metastasis. Cancer Sci 106(12):1669–1677

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Yoshizaki T, Kondo S, Wakisaka N, Murono S, Endo K, Sugimoto H, Nakanishi S, Tsuji A, Ito M (2013) Pathogenic role of Epstein-Barr virus latent membrane protein-1 in the development of nasopharyngeal carcinoma. Cancer Lett 337(1):1–7

    Article  CAS  PubMed  Google Scholar 

  78. Cha DJ, Franklin JL, Dou Y, Liu Q, Higginbotham JN, Demory Beckler M, Weaver AM, Vickers K, Prasad N, Levy S, Zhang B, Coffey RJ, Patton JG (2015) KRAS-dependent sorting of miRNA to exosomes. Elife 4:e07197

    Article  PubMed  PubMed Central  Google Scholar 

  79. Ramteke A, Ting H, Agarwal C, Mateen S, Somasagara R, Hussain A, Graner M, Frederick B, Agarwal R (2015) Deep G Exosomes secreted under hypoxia enhance invasiveness and stemness of prostate cancer cells by targeting adherens junction molecules. Mol Carcinog 54(7):554–65

    Article  CAS  PubMed  Google Scholar 

  80. Hou J, Wang F, Liu X (2018) Tumor-derived exosomes enhance invasion and metastasis of salivary adenoid cystic carcinoma cells. J Oral Pathol Med 47(2):144–151

    Article  CAS  PubMed  Google Scholar 

  81. Chowdhury R, Webber JP, Gurney M (2015) Cancer exosomes trigger mesenchymal stem cell differentiation into pro-angiogenic and pro-invasive myofibroblasts. Oncotarget 6(2):715–31

    Article  PubMed  Google Scholar 

  82. Zhao H, Yang L, Baddour J (2016) Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism. Elife 5:e10250

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  83. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674

    Article  CAS  PubMed  Google Scholar 

  84. Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100(1):57–70

    Article  CAS  PubMed  Google Scholar 

  85. Kucharzewska P, Christianson HC, Welch JE et al (2013) Exosomes reflect the hypoxic status of glioma cells and mediate hypoxia-dependent activation of vascular cells during tumor development. Proc Natl Acad Sci 110(18):7312–7317

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Grange C, Tapparo M, Collino F, Vitillo L, Damasco C, Deregibus MC, Tetta C, Bussolati B, Camussi G (2011) Microvesicles released from human renalcancer stem cells stimulate angiogenesis and formation of lung premetastaticniche. Cancer Res 71(15):5346

    Article  CAS  PubMed  Google Scholar 

  87. Psaila B, Lyden D et al (2009) The metastatic niche: adapting the foreign soil. Nat Rev Cancer 9(4):285–293

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Peinado H et al (2012) Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nat Med 18(6):883–891

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Hood JL et al (2011) Exosomes released by melanoma cells prepare sentinel lymph nodes for tumor metastasis. Cancer Res 71(11):3792–3801

    Article  CAS  PubMed  Google Scholar 

  90. Suetsugu A et al (2013) Imaging exosome transfer from breast cancer cells to stroma at metastatic sites in orthotopic nude-mouse models. Adv Drug Deliv Rev 65(3):383–390

    Article  CAS  PubMed  Google Scholar 

  91. Lobb RJ, Lima LG, Möller A (2017) Exosomes: key mediators of metastasis and pre-metastatic niche formation. Semin Cell Dev Biol 67:3–10

    Article  CAS  PubMed  Google Scholar 

  92. Segura E, Guérin C, Hogg N (2007) CD8+ dendritic cells use LFA-1 to capture MHC-peptide complexes from exosomes in vivo. J Immunol 179(3):1489–96

    Article  CAS  PubMed  Google Scholar 

  93. Morelli AE, Larregina AT, Shufesky WJ et al (2004) Endocytosis, intracellular sorting, and processing of exosomes by dendritic cells. Blood 104(10):3257–66

    Article  CAS  PubMed  Google Scholar 

  94. Hanayama R, Tanaka M, Miwa K (2002) Identification of a factor that links apoptotic cells to phagocytes. Nature 417(6885):182–7

    Article  CAS  PubMed  Google Scholar 

  95. Miyanishi M, Tada K, Koike M (2007) Identification of Tim4 as a phosphatidylserine receptor. Nature 450(7168):435–9

    Article  CAS  PubMed  Google Scholar 

  96. Saunderson SC, Dunn AC, Crocker PR (2014) CD169 mediates the capture of exosomes in spleen and lymph node. Blood 123(2):208–16

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Christianson HC, Svensson KJ, van Kuppevelt TH (2013) Cancer cell exosomes depend on cell-surface heparan sulfate proteoglycans for their internalization and functional activity. Proc Natl Acad Sci U S A 110(43):17380–5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Barrès C, Blanc L, Bette-Bobillo P (2010) Galectin-5 is bound onto the surface of rat reticulocyte exosomes and modulates vesicle uptake by macrophages. Blood 115(3):696–705

    Article  CAS  PubMed  Google Scholar 

  99. Rana S, Yue S, Stadel D (2012) Toward tailored exosomes: the exosomal tetraspanin web contributes to target cell selection. Int J Biochem Cell Biol 44(9):1574–84

    Article  CAS  PubMed  Google Scholar 

  100. Desgrosellier JS, Cheresh DA (2010) Integrins in cancer: biological implications and therapeutic opportunities. Nature Rev Cancer 10:9–22

    Article  CAS  Google Scholar 

  101. Bargatze RF, Butcher EC (1993) Rapid G protein-regulated activation event involved in lymphocyte binding to high endothelial venules. J Exp Med 178:367–72

    Article  CAS  PubMed  Google Scholar 

  102. Ebert LM, Schaerli P, Moser B (2005) Chemokine-mediated control of T cell traffic in lymphoid and peripheral tissues. Mol Immunol 42(7):799–809

    Article  CAS  PubMed  Google Scholar 

  103. Berlin C, Berg EL, Briskin MJ et al (1993) Alpha 4 beta 7 integrin mediates lymphocyte binding to the mucosal vascular addressin MAdCAM-1. Cell 74(1):185–95

    Article  CAS  PubMed  Google Scholar 

  104. Bargatze RF, Jutila MA, Butcher EC (1995) Distinct roles of L-selectin and integrins α4β7 and LFA-1 in lymphocyte homing to Peyer’s patch-HEV in situ: the multistep model confirmed and refined. Immunity 3:99–108

    Article  CAS  PubMed  Google Scholar 

  105. Park EJ, Prajuabjinda O, Soe ZY et al (2019) Exosomal regulation of lymphocyte homing to the gut. Blood Adv 3(1):1–11

    Article  CAS  PubMed  Google Scholar 

  106. Koni PA, Joshi SK, Temann UA, Olson D, Burkly L, Flavell RA (2001) Conditional vascular cell adhesion molecule 1 deletion in mice: impaired lymphocyte migration to bone marrow. J Exp Med 193:741–54

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Mazo IB, Honczarenko M, Leung H, Cavanagh LL, Bonasio R, Weninger W, Engelke K, Xia L, McEver RP, Koni PA, Silberstein LE, von Andrian UH (2005) Bone marrow is a major reservoir and site of recruitment for central memory CD8+ T cells. Immunity 22:259–70

    Article  CAS  PubMed  Google Scholar 

  108. Cepek KL, Shaw SK, Parker CM, Russell GJ, Morrow JS, Rimm DL, Brenner MB (1994) Adhesion between epithelial cells and T lymphocytes mediated by E-cadherin and the αEβ7 integrin. Nature 372:190–3

    Article  CAS  PubMed  Google Scholar 

  109. de Fougerolles AR, Sprague AG, Nickerson-Nutter CL et al (2000) Regulation of inflammation by collagen-binding integrins α1β1 and α2β1 in models of hypersensitivity and arthritis. J Clin Invest 105:721–9

    Article  PubMed  PubMed Central  Google Scholar 

  110. Engelhardt B, Ransohoff RM (2005) The ins and outs of T-lymphocyte trafficking to the CNS: anatomical sites and molecular mechanisms. Trends Immunol 26:485–95

    Article  CAS  PubMed  Google Scholar 

  111. Henninger DD, Panes J, Eppihimer M et al (1997) Cytokine induced VCAM-1 and ICAM-1 expression in different organs of the mouse. J Immunol 158:1825–32

    CAS  PubMed  Google Scholar 

  112. DeNucci CC, Mitchell JS, Shimizu Y (2009) Integrin function in t cell homing to lymphoid and non-lymphoid sites: getting there and staying there. Crit Rev Immunol 29(2):87–109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Campbell DJ, Butcher EC (2002) Rapid acquisition of tissue-specific homing phenotypes by CD4(+) T cells activated in cutaneous or mucosal lymphoid tissues. J Exp Med 195:135–141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Chen Q, Fisher DT, Clancy KA et al (2006) Fever-range thermal stress promotes lymphocyte trafficking across high endothelial venules via an interleukin 6 trans-signaling mechanism. Nat Immunol 7:1299–308

    Article  CAS  PubMed  Google Scholar 

  115. Abderrazak A, Syrovets T, Couchie D (2015) NLRP3 inflammasome: from a danger signal sensor to a regulatory node of oxidative stress and inflammatory diseases. Redox Biol 4:296–307

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. de Rivero Vaccari JP, Brand F 3rd, Adamczak S (2016) Exosome-mediated inflammasome signaling after central nervous system injury. J Neurochem 136(Suppl 1):39–48

    Article  CAS  PubMed  Google Scholar 

  117. Cai C, Koch B, Morikawa K (2018) Macrophage-derived extracellular vesicles induce long-lasting immunity against hepatitis c virus which is blunted by polyunsaturated fatty acids. Front Immunol 9:723

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  118. Lian Q, Xu J, Yan S et al (2017) Chemotherapy-induced intestinal inflammatory responses are mediated by exosome secretion of double-strand DNA via AIM2 inflammasome activation. Cell Res 27:784–800

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Ahn J, Barber GN (2014) Self-DNA, STING-dependent signaling and the origins of autoinflammatory disease. Curr Opin Immunol 31:121–126

    Article  CAS  PubMed  Google Scholar 

  120. Deng L, Liang H, Xu M et al (2014) STING-dependent cytosolic DNA sensing promotes radiation-induced type I interferon-dependent antitumor immunity in immunogenic tumors. Immunity 41:843–852

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Woo S-R, Fuertes Mercedes B, Corrales L et al (2014) STING-dependent cytosolic DNA sensing mediates innate immunerecognition of immunogenic tumors. Immunity 4:830–842

    Article  CAS  Google Scholar 

  122. Perelmuter VM, Manskikh VN (2012) Preniche as missing link of the metastatic niche concept explaining organ-preferential metastasis of malignant tumors and the type of metastatic disease. Biochemistry (Moscow) 77(1):111–118

    Article  CAS  Google Scholar 

  123. Hu Y, Yan C, Mu L et al (2015) Fibroblast-derived exosomes contribute to chemoresistance through priming cancer stem cells in colorectal cancer. Plos One 10:e0125625

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  124. Preta G, Cronin JG, Sheldon MI (2015) Dynasore - not just a dynamin inhibitor. Cell Commun Signal 13:24

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  125. Hazan-Halevy I, Rosenblum D, Weinstein S (2015) Cell-specific uptake of mantle cell lymphoma-derived exosomes by malignant and non-malignant B-lymphocytes. Cancer Lett 364(1):59–69

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Tian Y, Li S, Song J et al (2014) A doxorubicin delivery platform using engineered natural membrane vesicle exosomes for targeted tumor therapy. Biomaterials 35(7):2383–90

    Article  CAS  PubMed  Google Scholar 

  127. Kim MS, Haney MJ, Zhao Y et al (2016) Development of exosome-encapsulated paclitaxel to overcome MDR in cancer cells. Nanomedicine 12(3):655–664

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The study was supported by the Russian Science Foundation (Grant #19-75-30016).

Author information

Authors and Affiliations

  1. Department of Molecular Oncology and Immunology, Cancer Research Institute, Tomsk National Research Medical Center, Kooperativny Str. 5, Tomsk, 634050, Russian Federation

    E. S. Grigoryeva & N. V. Cherdyntseva

  2. Department of General and Molecular Pathology, Cancer Research Institute, Tomsk National Research Medical Center, Savinyh Str. 12/1, Tomsk, 634028, Russian Federation

    O. E. Savelieva & V. M. Perelmuter

  3. Department of Chemotherapy, Cancer Research Institute, Tomsk National Research Medical Center, Kooperativny Str. 5, Tomsk, 634050, Russian Federation

    N. O. Popova

Authors
  1. E. S. Grigoryeva
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. O. E. Savelieva
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. N. O. Popova
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. N. V. Cherdyntseva
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. V. M. Perelmuter
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to E. S. Grigoryeva.

Ethics declarations

Conflict of interest

The authors declare that there is no conflict of interest.

Ethcial approval

This article does not contain any studies involving animals/human participants performed by any of the authors.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Grigoryeva, E.S., Savelieva, O.E., Popova, N.O. et al. Do tumor exosome integrins alone determine organotropic metastasis?. Mol Biol Rep 47, 8145–8157 (2020). https://doi.org/10.1007/s11033-020-05826-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-020-05826-4

Keywords

Search

Navigation