Cellular and Molecular Life Sciences

, Volume 76, Issue 9, pp 1747–1758 | Cite as

Exosomes: from carcinogenesis and metastasis to diagnosis and treatment of gastric cancer

  • Houman Kahroba
  • Mohammad Saeid Hejazi
  • Nasser SamadiEmail author


Exosomes represent an important group of extracellular vesicles with a defined size between 40 and 150 nm and cup-shaped construction which have a pivotal role in elimination of intracellular debris and intercellular signaling networks. A line of evidence revealed the impact of different types of exosomes in initiation, progression, and metastasis of gastric cancer (GC). These bioactive vesicles mediate tumor and stromal communication network through modulation of cell signaling for carcinogenesis and pre-metastatic niche formation in distant organs. Exosomes contain various cargos including DNAs (mitochondrial and genomic), proteins, transposable elements, and RNAs (coding and noncoding) with different compositions related to functional status of origin cells. In this review, we summarize the main roles of key exosomal cargos in induction of exosome-mediated signaling in cancer cells. Body fluids are employed frequently as the source of exosomes released by tumor cells with a potential role in early diagnosis of GC and chemoresistance. These vesicles as non-toxic and non-immunogenic carriers are also found to be applied for novel drug delivery systems.


MiRNA Long non-coding RNA Signaling pathways Biomarker Chemoresistance Exosome-dependent drug delivery 



This work was supported by Tabriz university of medical sciences under Grant no. IR.TBZMED.REC.1396.910.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest


  1. 1.
    Sitarz R, Skierucha M, Mielko J et al (2018) Gastric cancer: epidemiology, prevention, classification, and treatment. Cancer Manag Res 10:239–248. CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Jeddi F, Soozangar N, Sadeghi MR et al (2018) Nrf2 overexpression is associated with P-glycoprotein upregulation in gastric cancer. Biomed Pharmacother 97:286–292. CrossRefPubMedGoogle Scholar
  3. 3.
    Smyth EC, Verheij M, Allum W et al (2016) Gastric cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up†. Ann Oncol 27:v38–v49. CrossRefPubMedGoogle Scholar
  4. 4.
    Yan Y, Fu G, Ye Y, Ming L (2017) Exosomes participate in the carcinogenesis and the malignant behavior of gastric cancer. Scand J Gastroenterol 52:499–504. CrossRefPubMedGoogle Scholar
  5. 5.
    Orditura M, Galizia G, Sforza V et al (2014) Treatment of gastric cancer. World J Gastroenterol 20:1635–1649. CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Shimizu D, Kanda M, Kodera Y (2018) Emerging evidence of the molecular landscape specific for hematogenous metastasis from gastric cancer. World J Gastrointest Oncol 10:124–136. CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Maia J, Caja S, Strano Moraes MC et al (2018) Exosome-based cell-cell communication in the tumor microenvironment. Front cell Dev Biol 6:18. CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Harding CV, Heuser JE, Stahl PD (2013) Exosomes: looking back three decades and into the future. J Cell Biol 200:367–371. CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Vlassov AV, Magdaleno S, Setterquist R, Conrad R (2012) Exosomes: current knowledge of their composition, biological functions, and diagnostic and therapeutic potentials. Biochim Biophys Acta 1820:940–948. CrossRefPubMedGoogle Scholar
  10. 10.
    Rajagopal C, Harikumar KB (2018) The origin and functions of exosomes in cancer. Front Oncol 8:66. CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Skotland T, Sandvig K, Llorente A (2017) Lipids in exosomes: current knowledge and the way forward. Prog Lipid Res 66:30–41. CrossRefPubMedGoogle Scholar
  12. 12.
    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:E968–E977. CrossRefPubMedGoogle Scholar
  13. 13.
    Ruivo CF, Adem B, Silva M, Melo SA (2017) The biology of cancer exosomes: insights and new perspectives. Cancer Res 77:6480–6488. CrossRefPubMedGoogle Scholar
  14. 14.
    Hessvik NP, Llorente A (2017) Current knowledge on exosome biogenesis and release. Cell Mol Life Sci. CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Yuyama K, Sun H, Mitsutake S, Igarashi Y (2012) Sphingolipid-modulated Exosome secretion promotes clearance of amyloid-β by microglia. J Biol Chem 287:10977–10989. CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Villarroya-Beltri C, Baixauli F, Mittelbrunn M et al (2016) ISGylation controls exosome secretion by promoting lysosomal degradation of MVB proteins. Nat Commun 7:13588. CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    McKelvey KJ, Powell KL, Ashton AW et al (2015) Exosomes: mechanisms of uptake. J Circ biomarkers 4:7. CrossRefGoogle Scholar
  18. 18.
    Zhang H-G, Grizzle WE (2014) Exosomes: a novel pathway of local and distant intercellular communication that facilitates the growth and metastasis of neoplastic lesions. Am J Pathol 184:28–41. CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Li X, Wang Y, Wang Q et al (2018) Exosomes in cancer: small transporters with big functions. Cancer Lett 435:55–65. CrossRefPubMedGoogle Scholar
  20. 20.
    Ludwig A-K, Giebel B (2012) Exosomes: small vesicles participating in intercellular communication. Int J Biochem Cell Biol 44:11–15. CrossRefPubMedGoogle Scholar
  21. 21.
    De Toro J, Herschlik L, Waldner C, Mongini C (2015) Emerging roles of exosomes in normal and pathological conditions: new insights for diagnosis and therapeutic applications. Front Immunol 6:203. CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Rana S, Malinowska K, Zöller M (2013) Exosomal tumor microRNA modulates premetastatic organ cells. Neoplasia 15:281–295CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Eyvazi S, Hejazi MS, Kahroba H et al (2018) Cdk9 as an appealing target for therapeutic interventions. Curr Drug Targets. CrossRefGoogle Scholar
  24. 24.
    Seo N, Shirakura Y, Tahara Y et al (2018) Activated CD8 + T cell extracellular vesicles prevent tumour progression by targeting of lesional mesenchymal cells. Nat Commun 9:435. CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Brinton L, Sloane H, Kester M, Kelly K (2015) Formation and role of exosomes in cancer. Cell Mol Life 72:659–671CrossRefGoogle Scholar
  26. 26.
    Imamura T, Komatsu S, Ichikawa D et al (2017) Low plasma levels of miR-101 are associated with tumor progression in gastric cancer. Oncotarget 8:106538–106550. CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Wang M, Zhao C, Shi H et al (2014) Deregulated microRNAs in gastric cancer tissue-derived mesenchymal stem cells: novel biomarkers and a mechanism for gastric cancer. Br J Cancer 110:1199CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Li W, Gao Y-Q (2018) MiR-217 is involved in the carcinogenesis of gastric cancer by down-regulating CDH1 expression. Kaohsiung J Med Sci 34:377–384. CrossRefPubMedGoogle Scholar
  29. 29.
    Ohshima K, Inoue K, Fujiwara A et al (2010) Let-7 MicroRNA family is selectively secreted into the extracellular environment via exosomes in a metastatic gastric cancer cell line. PLoS One 5:e13247. CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Ke X, Yan R, Sun Z et al (2017) Esophageal adenocarcinoma-derived extracellular vesicle microRNAs induce a neoplastic phenotype in gastric organoids. Neoplasia 19:941–949. CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Qu J-L, Qu X-J, Zhao M-F et al (2009) Gastric cancer exosomes promote tumour cell proliferation through PI3K/Akt and MAPK/ERK activation. Dig Liver Dis 41:875–880. CrossRefPubMedGoogle Scholar
  32. 32.
    Li C, Liu D, Li G et al (2015) CD97 promotes gastric cancer cell proliferation and invasion through exosome-mediated MAPK signaling pathway. World J Gastroentrol 21:6215CrossRefGoogle Scholar
  33. 33.
    Qi J, Zhou Y, Jiao Z et al (2017) Exosomes derived from human bone marrow mesenchymal stem cells promote tumor growth through hedgehog signaling pathway. Cell Physiol Biochem 42:2242–2254. CrossRefPubMedGoogle Scholar
  34. 34.
    Valastyan S, Weinberg RA (2011) Tumor metastasis: molecular insights and evolving paradigms. Cell 147:275–292. CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Sawayama H, Ishimoto T, Baba H (2018) Microenvironment in the pathogenesis of gastric cancer metastasis. J Cancer Metastasis Treat 4:10. CrossRefGoogle Scholar
  36. 36.
    Arita T, Ichikawa D, Konishi H et al (2016) Tumor exosome-mediated promotion of adhesion to mesothelial cells in gastric cancer cells. Oncotarget 7:56855–56863. CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Chen K-B, Chen J, Jin X-L et al (2018) Exosome-mediated peritoneal dissemination in gastric cancer and its clinical applications. Biomed Rep 8:503–509. CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Tokuhisa M, Ichikawa Y, Kosaka N et al (2015) Exosomal miRNAs from peritoneum lavage fluid as potential prognostic biomarkers of peritoneal metastasis in gastric cancer. PLoS One 10:e0130472. CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Zhang X, Shi H, Yuan X et al (2018) Tumor-derived exosomes induce N2 polarization of neutrophils to promote gastric cancer cell migration. Mol Cancer 17:146. CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Yang H, Zhang H, Ge S et al (2018) Exosome-derived miR-130a activates angiogenesis in gastric cancer by targeting C-MYB in vascular endothelial cells. Mol Ther 26:2466–2475. CrossRefPubMedGoogle Scholar
  41. 41.
    Fallah A, Sadeghinia A, Kahroba H et al (2019) Therapeutic targeting of angiogenesis molecular pathways in angiogenesis-dependent diseases. Biomed Pharmacother 110:775–785. CrossRefPubMedGoogle Scholar
  42. 42.
    Tsai JH, Yang J (2013) Epithelial-mesenchymal plasticity in carcinoma metastasis. Genes Dev 27:2192–2206. CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Diepenbruck M, Christofori G (2016) Epithelial–mesenchymal transition (EMT) and metastasis: yes, no, maybe? Curr Opin Cell Biol 43:7–13. CrossRefPubMedGoogle Scholar
  44. 44.
    Yang H, Fu H, Wang B et al (2018) Exosomal miR-423-5p targets SUFU to promote cancer growth and metastasis and serves as a novel marker for gastric cancer. Mol Carcinog. CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Steinbichler TB, Dudás J, Riechelmann H, Skvortsova I-I (2017) The role of exosomes in cancer metastasis. Semin Cancer Biol 44:170–181. CrossRefPubMedGoogle Scholar
  46. 46.
    Gu H, Ji R, Zhang X, Wang M (2016) Exosomes derived from human mesenchymal stem cells promote gastric cancer cell growth and migration via the activation of the Akt pathway. Mol Med Rep 14:3452–3458CrossRefPubMedGoogle Scholar
  47. 47.
    Tao L, Huang G, Song H et al (2017) Cancer associated fibroblasts: an essential role in the tumor microenvironment. Oncol Lett 14:2611–2620. CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Wang J, Guan X, Zhang Y et al (2018) Exosomal miR-27a derived from gastric cancer cells regulates the transformation of fibroblasts into cancer-associated fibroblasts. Cell Physiol Biochem 49:I. CrossRefGoogle Scholar
  49. 49.
    Gu J, Qian H, Shen L et al (2012) Gastric cancer exosomes trigger differentiation of umbilical cord derived mesenchymal stem cells to carcinoma-associated fibroblasts through TGF-β/Smad pathway. PLoS One 7:e52465. CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Ning X, Zhang H, Wang C, Song X (2018) Exosomes released by gastric cancer cells induce transition of pericytes into cancer-associated fibroblasts. Med Sci Monit 24:2350–2359CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Ma M, Chen S, Liu Z et al (2017) miRNA-221 of exosomes originating from bone marrow mesenchymal stem cells promotes oncogenic activity in gastric cancer. Onco Targets Ther 10:4161–4171. CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Zhu W, Huang L, Li Y et al (2012) Exosomes derived from human bone marrow mesenchymal stem cells promote tumor growth in vivo. Cancer Lett 315:28–37CrossRefPubMedGoogle Scholar
  53. 53.
    Zheng X, Turkowski K, Mora J et al (2017) Redirecting tumor-associated macrophages to become tumoricidal effectors as a novel strategy for cancer therapy. Oncotarget 8:4843–48452. CrossRefGoogle Scholar
  54. 54.
    Wu L, Zhang X, Zhang B et al (2016) Exosomes derived from gastric cancer cells activate NF-κB pathway in macrophages to promote cancer progression. Tumor Biol 37:12169–12180CrossRefGoogle Scholar
  55. 55.
    Wang F, Li B, Wei Y et al (2018) Tumor-derived exosomes induce PD1 + macrophage population in human gastric cancer that promotes disease progression. Oncogenesis 7:41. CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Zheng P, Luo Q, Wang W et al (2018) Tumor-associated macrophages-derived exosomes promote the migration of gastric cancer cells by transfer of functional Apolipoprotein E. Cell Death Dis 94(9):434. CrossRefGoogle Scholar
  57. 57.
    Yamamoto H (2014) Detection of DNA methylation of gastric juice-derived exosomes in gastric cancer. Integr Mol Med 1:17–21. CrossRefGoogle Scholar
  58. 58.
    Yamamoto H, Watanabe Y, Oikawa R et al (2016) BARHL2 methylation using gastric wash DNA or gastric juice exosomal DNA is a useful marker for early detection of gastric cancer in an H. pylori-independent manner. Clin Transl Gastroenterol 7:e184. CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Chen Y, Xie Y, Xu L et al (2017) Protein content and functional characteristics of serum-purified exosomes from patients with colorectal cancer revealed by quantitative proteomics. Int J Cancer 140:900–913. CrossRefPubMedGoogle Scholar
  60. 60.
    Miki Y, Yashiro M, Okuno T et al (2018) CD9-positive exosomes from cancer-associated fibroblasts stimulate the migration ability of scirrhous-type gastric cancer cells. Br J Cancer 118:867–877. CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Yoon JH, Ham I-H, Kim O et al (2018) Gastrokine 1 protein is a potential theragnostic target for gastric cancer. Gastric Cancer. CrossRefPubMedGoogle Scholar
  62. 62.
    Fu H, Yang H, Zhang X et al (2018) Exosomal TRIM3 is a novel marker and therapy target for gastric cancer. J Exp Clin Cancer Res 37:162. CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Yen E-Y, Miaw S-C, Yu J-S, Lai I-R (2017) Exosomal TGF-β1 is correlated with lymphatic metastasis of gastric cancers. Am J Cancer Res 7:2199–2208PubMedPubMedCentralGoogle Scholar
  64. 64.
    Anami K, Oue N, Noguchi T et al (2016) TSPAN8, identified by Escherichia coli ampicillin secretion trap, is associated with cell growth and invasion in gastric cancer. Gastric Cancer 19:370–380. CrossRefPubMedGoogle Scholar
  65. 65.
    Zhang H, Deng T, Liu R et al (2017) Exosome-delivered EGFR regulates liver microenvironment to promote gastric cancer liver metastasis. Nat Commun 8:15016. CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Chen K-B, Chen J, Jin X-L et al (2018) Exosome-mediated peritoneal dissemination in gastric cancer and its clinical applications. Biomed reports 8:503–509. CrossRefGoogle Scholar
  67. 67.
    Wang J-P, Tang Y-Y, Fan C-M et al (2018) The role of exosomal non-coding RNAs in cancer metastasis. Oncotarget 9:12487–12502. CrossRefPubMedGoogle Scholar
  68. 68.
    Majidinia M, Yousefi B (2016) Long non-coding RNAs in cancer drug resistance development. DNA Repair (Amst) 45:25–33. CrossRefGoogle Scholar
  69. 69.
    Zhao R, Zhang Y, Zhang X et al (2018) Exosomal long noncoding RNA HOTTIP as potential novel diagnostic and prognostic biomarker test for gastric cancer. Mol Cancer 17:68. CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Liu X, Sun M, Nie F et al (2014) Lnc RNA HOTAIR functions as a competing endogenous RNA to regulate HER2 expression by sponging miR-331-3p in gastric cancer. Mol Cancer 13:92. CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Li Q, Shao Y, Zhang X et al (2015) Plasma long noncoding RNA protected by exosomes as a potential stable biomarker for gastric cancer. Tumor Biol 36:2007–2012CrossRefGoogle Scholar
  72. 72.
    Pan L, Liang W, Fu M et al (2017) Exosomes-mediated transfer of long noncoding RNA ZFAS1 promotes gastric cancer progression. J Cancer Res Clin Oncol 143:991–1004. CrossRefPubMedGoogle Scholar
  73. 73.
    Huang Y, Luo H, Li F et al (2018) LINC00152 down-regulated miR-193a-3p to enhance MCL1 expression and promote gastric cancer cells proliferation. Biosci Rep 38:BSR20171607.
  74. 74.
    Huang Y, Zhang J, Hou L et al (2017) LncRNA AK023391 promotes tumorigenesis and invasion of gastric cancer through activation of the PI3K/Akt signaling pathway. J Exp Clin Cancer Res 36:194. CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Dong D, Mu Z, Zhao C, Sun M (2018) ZFAS1: a novel tumor-related long non-coding RNA. Cancer Cell Int 18:125. CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Majidinia M, Darband SG, Kaviani M et al (2018) Cross-regulation between Notch signaling pathway and miRNA machinery in cancer. DNA Repair (Amst) 66–67:30–41. CrossRefGoogle Scholar
  77. 77.
    Zhang X, Liang W, Liu J et al (2018) Long non-coding RNA UFC1 promotes gastric cancer progression by regulating miR-498/Lin28b. J Exp Clin Cancer Res 37:134. CrossRefPubMedPubMedCentralGoogle Scholar
  78. 78.
    Shimoda A, Ueda K, Nishiumi S (2016) Exosomes as nanocarriers for systemic delivery of the Helicobacter pylori virulence factor CagA. Sci Rep 6:18346CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Zhang W, Jiang X, Bao J et al (2018) Exosomes in pathogen infections: a bridge to deliver molecules and link functions. Front Immunol 9:90. CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Che Y, Geng B, Xu Y et al (2018) Helicobacter pylori-induced exosomal MET educates tumour-associated macrophages to promote gastric cancer progression. J Cell Mol Med 22:5708–5719. CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    Polakovicova I, Jerez S, Wichmann IA et al (2018) Role of microRNAs and exosomes in Helicobacter pylori and Epstein-barr virus associated gastric cancers. Front Microbiol 9:636. CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Wang J, Wang Q, Liu H et al (2010) MicroRNA expression and its implication for the diagnosis and therapeutic strategies of gastric cancer. Cancer Lett 29:7137–7143Google Scholar
  83. 83.
    Jarry J, Schadendorf D, Greenwood C et al (2014) The validity of circulating microRNAs in oncology: five years of challenges and contradictions. Mol Oncol 8:819–829. CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    Ueda T, Volinia S, Okumura H et al (2010) Relation between microRNA expression and progression and prognosis of gastric cancer: a microRNA expression analysis. Lancet Oncol 11:136–146. CrossRefPubMedGoogle Scholar
  85. 85.
    Rosenfeld N, Aharonov R, Meiri E et al (2008) MicroRNAs accurately identify cancer tissue origin. Nat Biotechnol 26:462–469. CrossRefPubMedGoogle Scholar
  86. 86.
    Huang Z, Zhu D, Wu L et al (2017) Six serum-based miRNAs as potential diagnostic biomarkers for gastric cancer. Cancer Epidemiol Biomarkers Prev 26:188–196. CrossRefPubMedGoogle Scholar
  87. 87.
    Tokuhisa M, Ichikawa Y, Kosaka N, Ochiya T (2015) Exosomal miRNAs from peritoneum lavage fluid as potential prognostic biomarkers of peritoneal metastasis in gastric cancer. PLoS One 10:e130472CrossRefGoogle Scholar
  88. 88.
    Kumata Y, Iinuma H, Suzuki Y et al (2018) Exosome-encapsulated microRNA-23b as a minimally invasive liquid biomarker for the prediction of recurrence and prognosis of gastric cancer patients in each tumor stage. Oncol Rep 40:319–330. CrossRefPubMedGoogle Scholar
  89. 89.
    Lin L-Y, Yang L, Zeng Q et al (2018) Tumor-originated exosomal lncUEGC1 as a circulating biomarker for early-stage gastric cancer. Mol Cancer 17:84. CrossRefPubMedPubMedCentralGoogle Scholar
  90. 90.
    Berrondo C, Flax J, Kucherov V et al (2016) Expression of the long non-coding RNA HOTAIR correlates with disease progression in bladder cancer and is contained in bladder cancer patient urinary exosomes. PLoS One 11:e0147236. CrossRefPubMedPubMedCentralGoogle Scholar
  91. 91.
    Li W, Li C, Zhou T et al (2017) Role of exosomal proteins in cancer diagnosis. Mol Cancer 16:145. CrossRefPubMedPubMedCentralGoogle Scholar
  92. 92.
    Abak A, Abhari A, Rahimzadeh S (2018) Exosomes in cancer: small vesicular transporters for cancer progression and metastasis, biomarkers in cancer therapeutics. Peer J 6:e4763. CrossRefPubMedGoogle Scholar
  93. 93.
    Rocha CRR, Silva MM, Quinet A et al (2018) DNA repair pathways and cisplatin resistance: an intimate relationship. Clinics (Sao Paulo) 73:e478s. CrossRefGoogle Scholar
  94. 94.
    Jeddi F, Soozangar N, Sadeghi MR et al (2017) Contradictory roles of Nrf2/Keap1 signaling pathway in cancer prevention/promotion and chemoresistance. DNA Repair (Amst) 54:13–21. CrossRefGoogle Scholar
  95. 95.
    Ratti M, Lampis A, Hahne JC et al (2018) Microsatellite instability in gastric cancer: molecular bases, clinical perspectives, and new treatment approaches. Cell Mol Life Sci 75:4151–4162. CrossRefPubMedPubMedCentralGoogle Scholar
  96. 96.
    Zhou J, Tan X, Tan Y et al (2018) Mesenchymal stem cell derived exosomes in cancer progression, metastasis and drug delivery: a comprehensive review. J Cancer 9:3129–3137. CrossRefPubMedPubMedCentralGoogle Scholar
  97. 97.
    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. CrossRefPubMedPubMedCentralGoogle Scholar
  98. 98.
    Dianat-Moghadam H, Heydarifard M, Jahanban-Esfahlan R et al (2018) Cancer stem cells-emanated therapy resistance: implications for liposomal drug delivery systems. J Control Release 288:62–83. CrossRefPubMedGoogle Scholar
  99. 99.
    Zheng P, Chen L, Yuan X et al (2017) Exosomal transfer of tumor-associated macrophage-derived miR-21 confers cisplatin resistance in gastric cancer cells. J Exp Clin Cancer Res 36:53. CrossRefPubMedPubMedCentralGoogle Scholar
  100. 100.
    Wang X, Zhang H, Bai M et al (2018) Exosomes serve as nanoparticles to deliver anti-miR-214 to reverse chemoresistance to cisplatin in gastric cancer. Mol Ther 26:774–783. CrossRefPubMedPubMedCentralGoogle Scholar
  101. 101.
    Wang J-J, Wang Z-Y, Chen R et al (2015) Macrophage-secreted Exosomes delivering miRNA-21 inhibitor can regulate BGC-823 cell proliferation. Asian Pac J Cancer Prev 16:4203–4209CrossRefPubMedGoogle Scholar
  102. 102.
    Barok M, Puhka M, Vereb G et al (2018) Cancer-derived exosomes from HER2-positive cancer cells carry trastuzumab-emtansine into cancer cells leading to growth inhibition and caspase activation. BMC Cancer 18:504. CrossRefPubMedPubMedCentralGoogle Scholar
  103. 103.
    Zhang H, Wang Y, Bai M et al (2018) Exosomes serve as nanoparticles to suppress tumor growth and angiogenesis in gastric cancer by delivering hepatocyte growth factor siRNA. Cancer Sci 109:629–641. CrossRefPubMedPubMedCentralGoogle Scholar
  104. 104.
    Kahn S, Liao Y, Du X et al (2018) Exosomal MicroRNAs in milk from mothers delivering preterm infants survive in vitro digestion and are taken up by human intestinal cells. Mol Nutr Food Res 62:1701050. CrossRefGoogle Scholar

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Molecular Medicine Research CenterTabriz University of Medical SciencesTabrizIran
  2. 2.Department of Molecular Medicine, Faculty of Advanced Medical SciencesTabriz University of Medical SciencesTabrizIran
  3. 3.Department of Pharmaceutical Biotechnology, Faculty of PharmacyTabriz University of Medical SciencesTabrizIran
  4. 4.Department of Biochemistry, Faculty of MedicineTabriz University of Medical SciencesTabrizIran

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