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Exosomes: Mediators and Therapeutic Targets of Diabetes and Pancreatic Cancer

  • Deepak KGK
  • Rama Rao MallaEmail author
Chapter

Abstract

Exosomes are nanoscale extracellular vesicles secreted by exocytosis and affect both physiological and pathological mechanisms. Exosomes are important mediators and therapeutic targets of diabetes mellitus and pancreatic cancer owing to their role in controlling β-cell mass and insulin signaling. Early diagnosis of diabetes and pancreatic cancer can remarkably expand therapeutic approaches and overall survival. Further, identification of biomarkers for predicting the risk of diabetes and pancreatic cancer development and monitoring of their progression to disease state could be useful in envisaging possible complications along with prevention and treatment. Recently, exosomes are recognized as apparent facilitators of intercellular communication. They are reported as novel source of potential biomarkers. Current knowledge on exosome content can further aid in the development of potential markers for diagnosis and prognosis of diabetes and pancreatic cancer and also for discovery of novel therapeutic targets. This chapter covers the current updates on the role of exosomes in types 1 and 2 diabetes as well as pancreatic cancer. The later sections cover the role of exosome in diagnosis, drug delivery, and treatment of diabetes and pancreatic cancer along with their future prospects.

Keywords

Apoptosis Biomarkers Diabetes Exosomes MicroRNA and pancreatic cancer 

Abbreviations

ADSCs

Adipose-derived stem cells

CSF

Cerebrospinal fluid

DC

Dendritic cells

LADA

Latent autoimmune diabetes

MODY

Monogenic maturity onset diabetes

MSC

Mesenchymal stem cell

PP cells

Pancreatic polypeptide cells

RI

Resistance to insulin

T1D

Type I diabetes

T2D

Type II diabetes

References

  1. 1.
    Zhang Y, Liu Y, Liu H, Tang WH (2019) Exosomes: biogenesis, biologic function and clinical potential. Cell Biosci 9:19PubMedPubMedCentralGoogle Scholar
  2. 2.
    Menay F, Herschlik L, De Toro J, Cocozza F, Tsacalian R, Gravisaco MJ, Di Sciullo MP, Vendrell A, Waldner CI, Mongini C (2017) Exosomes isolated from ascites of T-cell lymphoma-bearing mice expressing surface CD24 and HSP-90 induce a tumor-specific immune response. Front Immunol 8:286PubMedPubMedCentralGoogle Scholar
  3. 3.
    Willms E, Johansson HJ, Mager I, Lee Y, Blomberg KE, Sadik M, Alaarg A, Smith CI, Lehtio J, El Andaloussi S, Wood MJ, Vader P (2016) Cells release subpopulations of exosomes with distinct molecular and biological properties. Sci Rep 6:22519PubMedPubMedCentralGoogle Scholar
  4. 4.
    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 6:18PubMedPubMedCentralGoogle Scholar
  5. 5.
    Wu R, Gao W, Yao K, Ge J (2019) Roles of exosomes derived from immune cells in cardiovascular diseases. Front Immunol 10:648PubMedPubMedCentralGoogle Scholar
  6. 6.
    Silva AM, Teixeira JH, Almeida MI, Goncalves RM, Barbosa MA, Santos SG (2017) Extracellular vesicles: immunomodulatory messengers in the context of tissue repair/regeneration. Eur J Pharm Sci 98:86–95PubMedGoogle Scholar
  7. 7.
    Anel A, Gallego-Lleyda A, de Miguel D, Naval J, Martinez-Lostao L (2019) Role of exosomes in the regulation of T-cell mediated immune responses and in autoimmune disease. Cells 8(2):E154PubMedGoogle Scholar
  8. 8.
    Gao D, Jiang L (2018) Exosomes in cancer therapy: a novel experimental strategy. Am J Cancer Res 8:2165–2175PubMedPubMedCentralGoogle Scholar
  9. 9.
    Zhang C, Ji Q, Yang Y, Li Q, Wang Z (2018) Exosome: function and role in Cancer metastasis and drug resistance. Technol Cancer Res Treat 17:1533033818763450PubMedPubMedCentralGoogle Scholar
  10. 10.
    Geis-Asteggiante L, Belew AT, Clements VK, Edwards NJ, Ostrand-Rosenberg S, El-Sayed NM, Fenselau C (2018) Differential content of proteins, mRNAs, and miRNAs suggests that MDSC and their exosomes may mediate distinct immune suppressive functions. J Proteome Res 17:486–498PubMedGoogle Scholar
  11. 11.
    Malla RR, Pandrangi S, Kumari S, Gavara MM, Badana AK (2018) Exosomal tetraspanins as regulators of cancer progression and metastasis and novel diagnostic markers. Asia Pac J Clin Oncol 14:383–391PubMedGoogle Scholar
  12. 12.
    Yang Q, Diamond MP, Al-Hendy A (2016) The emerging role of extracellular vesicle-derived miRNAs: implication in cancer progression and stem cell related diseases. J Clin Epigenet 2(1):13PubMedPubMedCentralGoogle Scholar
  13. 13.
    Willms E, Cabanas C, Mager I, Wood MJA, Vader P (2018) Extracellular vesicle heterogeneity: subpopulations, isolation techniques, and diverse functions in cancer progression. Front Immunol 9:738PubMedPubMedCentralGoogle Scholar
  14. 14.
    Yan Y, Fu G, Ming L (2018) Role of exosomes in pancreatic cancer. Oncol Lett 15:7479–7488PubMedPubMedCentralGoogle Scholar
  15. 15.
    Guay C, Regazzi R (2017) Exosomes as new players in metabolic organ cross-talk. Diabetes Obes Metab 19(Suppl 1):137–146Google Scholar
  16. 16.
    Tan L, Wu H, Liu Y, Zhao M, Li D, Lu Q (2016) Recent advances of exosomes in immune modulation and autoimmune diseases. Autoimmunity 49:357–365PubMedGoogle Scholar
  17. 17.
    Garcia-Contreras M, Brooks RW, Boccuzzi L, Robbins PD, Ricordi C (2017) Exosomes as biomarkers and therapeutic tools for type 1 diabetes mellitus. Eur Rev Med Pharmacol Sci 21:2940–2956PubMedGoogle Scholar
  18. 18.
    Cabrera O, Berman DM, Kenyon NS, Ricordi C, Berggren PO, Caicedo A (2006) The unique cytoarchitecture of human pancreatic islets has implications for islet cell function. Proc Natl Acad Sci U S A 103:2334–2339PubMedPubMedCentralGoogle Scholar
  19. 19.
    Figliolini F, Cantaluppi V, De Lena M, Beltramo S, Romagnoli R, Salizzoni M, Melzi R, Nano R, Piemonti L, Tetta C, Biancone L, Camussi G (2014) Isolation, characterization and potential role in Beta cell-endothelium cross-talk of extracellular vesicles released from human pancreatic islets. PLoS One 9:e102521PubMedPubMedCentralGoogle Scholar
  20. 20.
    Koh DS, Cho JH, Chen L (2012) Paracrine interactions within islets of Langerhans. J Mol Neurosci 48:429–440PubMedGoogle Scholar
  21. 21.
    Bennet WM, Wang ZL, Jones PM, Wang RM, James RF, London NJ, Ghatei MA, Bloom SR (1996) Presence of neuropeptide Y and its messenger ribonucleic acid in human islets: evidence for a possible paracrine role. J Clin Endocrinol Metab 81:2117–2120PubMedGoogle Scholar
  22. 22.
    Rodriguez-Diaz R, Menegaz D, Caicedo A (2014) Neurotransmitters act as paracrine signals to regulate insulin secretion from the human pancreatic islet. J Physiol 592:3413–3417PubMedPubMedCentralGoogle Scholar
  23. 23.
    Guay C, Menoud V, Rome S, Regazzi R (2015) Horizontal transfer of exosomal microRNAs transduce apoptotic signals between pancreatic beta-cells. Cell Commun Signal 13:17PubMedCentralGoogle Scholar
  24. 24.
    Lee HS, Jeong J, Lee KJ (2009) Characterization of vesicles secreted from insulinoma NIT-1 cells. J Proteome Res 8:2851–2862PubMedGoogle Scholar
  25. 25.
    Palmisano G, Jensen SS, Le Bihan MC, Laine J, McGuire JN, Pociot F, Larsen MR (2012) Characterization of membrane-shed microvesicles from cytokine-stimulated beta-cells using proteomics strategies. Mol Cell Proteomics 11:230–243PubMedPubMedCentralGoogle Scholar
  26. 26.
    Zhu Q, Kang J, Miao H, Feng Y, Xiao L, Hu Z, Liao DF, Huang Y, Jin J, He S (2014) Low-dose cytokine-induced neutral ceramidase secretion from INS-1 cells via exosomes and its anti-apoptotic effect. FEBS J 281:2861–2870PubMedGoogle Scholar
  27. 27.
    Ibrahim M, Tuomilehto J, Aschner P, Beseler L, Cahn A, Eckel RH, Fischl AH, Guthrie G, Hill JO, Kumwenda M, Leslie RD, Olson DE, Pozzilli P, Weber SL, Umpierrez GE (2018) Global status of diabetes prevention and prospects for action: a consensus statement. Diabetes Metab Res Rev 34:e3021PubMedGoogle Scholar
  28. 28.
    Kharroubi AT, Darwish HM (2015) Diabetes mellitus: the epidemic of the century. World J Diabetes 6:850–867PubMedPubMedCentralGoogle Scholar
  29. 29.
    Kahn BB, Flier JS (2000) Obesity and insulin resistance. J Clin Invest 106:473–481PubMedCentralGoogle Scholar
  30. 30.
    Yoon JW, Jun HS (2005) Autoimmune destruction of pancreatic beta cells. Am J Ther 12:580–591PubMedGoogle Scholar
  31. 31.
    Wang Z, Xie Z, Lu Q, Chang C, Zhou Z (2017) Beyond genetics: what causes type 1 diabetes. Clin Rev Allergy Immunol 52:273–286PubMedGoogle Scholar
  32. 32.
    Durinovic-Bello I (1998) Autoimmune diabetes: the role of T cells. Autoimmunity 27:159–177PubMedGoogle Scholar
  33. 33.
    McGinty JW, Marre ML, Bajzik V, Piganelli JD, James EA (2015) T cell epitopes and post-translationally modified epitopes in type 1 diabetes. Curr Diab Rep 15:90PubMedPubMedCentralGoogle Scholar
  34. 34.
    Delong T, Wiles TA, Baker RL, Bradley B, Barbour G, Reisdorph R, Armstrong M, Powell RL, Reisdorph N, Kumar N, Elso CM, DeNicola M, Bottino R, Powers AC, Harlan DM, Kent SC, Mannering SI, Haskins K (2016) Pathogenic CD4 T cells in type 1 diabetes recognize epitopes formed by peptide fusion. Science (New York, NY) 351:711–714Google Scholar
  35. 35.
    Sheng H, Hassanali S, Nugent C, Wen L, Hamilton-Williams E, Dias P, Dai YD (1950) Insulinoma-released exosomes or microparticles are immunostimulatory and can activate autoreactive T cells spontaneously developed in nonobese diabetic mice. J Immunol (Baltimore, MD) 187(2011):1591–1600Google Scholar
  36. 36.
    Bashratyan R, Sheng H, Regn D, Rahman MJ, Dai YD (2013) Insulinoma-released exosomes activate autoreactive marginal zone-like B cells that expand endogenously in prediabetic NOD mice. Eur J Immunol 43:2588–2597PubMedGoogle Scholar
  37. 37.
    Vomund AN, Zinselmeyer BH, Hughes J, Calderon B, Valderrama C, Ferris ST, Wan X, Kanekura K, Carrero JA, Urano F, Unanue ER (2015) Beta cells transfer vesicles containing insulin to phagocytes for presentation to T cells. Proc Natl Acad Sci U S A 112:E5496–E5502PubMedPubMedCentralGoogle Scholar
  38. 38.
    Butler AE, Janson J, Bonner-Weir S, Ritzel R, Rizza RA, Butler PC (2003) Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes 52:102–110PubMedGoogle Scholar
  39. 39.
    Ge Q, Gerard J, Noel L, Scroyen I, Brichard SM (2012) MicroRNAs regulated by adiponectin as novel targets for controlling adipose tissue inflammation. Endocrinology 153:5285–5296PubMedGoogle Scholar
  40. 40.
    Thomou T, Mori MA, Dreyfuss JM, Konishi M, Sakaguchi M, Wolfrum C, Rao TN, Winnay JN, Garcia-Martin R, Grinspoon SK, Gorden P, Kahn CR (2017) Adipose-derived circulating miRNAs regulate gene expression in other tissues. Nature 542:450–455PubMedPubMedCentralGoogle Scholar
  41. 41.
    Jayabalan N, Nair S, Nuzhat Z, Rice GE, Zuniga FA, Sobrevia L, Leiva A, Sanhueza C, Gutierrez JA, Lappas M, Freeman DJ, Salomon C (2017) Cross talk between adipose tissue and placenta in obese and gestational diabetes mellitus pregnancies via exosomes. Front Endocrinol 8:239Google Scholar
  42. 42.
    Herder C, Schneitler S, Rathmann W, Haastert B, Schneitler H, Winkler H, Bredahl R, Hahnloser E, Martin S (2007) Low-grade inflammation, obesity, and insulin resistance in adolescents. J Clin Endocrinol Metab 92:4569–4574PubMedGoogle Scholar
  43. 43.
    Kranendonk ME, Visseren FL, van Balkom BW, Nolte-’t Hoen EN, van Herwaarden JA, de Jager W, Schipper HS, Brenkman AB, Verhaar MC, Wauben MH, Kalkhoven E (2014) Human adipocyte extracellular vesicles in reciprocal signaling between adipocytes and macrophages. Obesity (Silver Spring, Md) 22:1296–1308Google Scholar
  44. 44.
    Deng ZB, Poliakov A, Hardy RW, Clements R, Liu C, Liu Y, Wang J, Xiang X, Zhang S, Zhuang X, Shah SV, Sun D, Michalek S, Grizzle WE, Garvey T, Mobley J, Zhang HG (2009) Adipose tissue exosome-like vesicles mediate activation of macrophage-induced insulin resistance. Diabetes 58:2498–2505PubMedPubMedCentralGoogle Scholar
  45. 45.
    Ying W, Riopel M, Bandyopadhyay G, Dong Y, Birmingham A, Seo JB, Ofrecio JM, Wollam J, Hernandez-Carretero A, Fu W, Li P, Olefsky JM (2017) Adipose tissue macrophage-derived exosomal miRNAs can modulate in vivo and in vitro insulin sensitivity. Cell 171:372–384.e312PubMedGoogle Scholar
  46. 46.
    Yu Y, Du H, Wei S, Feng L, Li J, Yao F, Zhang M, Hatch GM, Chen L (2018) Adipocyte-derived exosomal MiR-27a induces insulin resistance in skeletal muscle through repression of PPARgamma. Theranostics 8:2171–2188PubMedPubMedCentralGoogle Scholar
  47. 47.
    Kranendonk ME, Visseren FL, van Herwaarden JA, Nolte-’t Hoen EN, de Jager W, Wauben MH, Kalkhoven E (2014) Effect of extracellular vesicles of human adipose tissue on insulin signaling in liver and muscle cells. Obesity (Silver Spring, Md) 22:2216–2223Google Scholar
  48. 48.
    Vallabhajosyula P, Korutla L, Habertheuer A, Yu M, Rostami S, Yuan CX, Reddy S, Liu C, Korutla V, Koeberlein B, Trofe-Clark J, Rickels MR, Naji A (2017) Tissue-specific exosome biomarkers for noninvasively monitoring immunologic rejection of transplanted tissue. J Clin Invest 127:1375–1391PubMedPubMedCentralGoogle Scholar
  49. 49.
    Kalani A, Mohan A, Godbole MM, Bhatia E, Gupta A, Sharma RK, Tiwari S (2013) Wilm’s tumor-1 protein levels in urinary exosomes from diabetic patients with or without proteinuria. PLoS One 8:e60177PubMedPubMedCentralGoogle Scholar
  50. 50.
    Musante L, Tataruch D, Gu D, Liu X, Forsblom C, Groop PH, Holthofer H (2015) Proteases and protease inhibitors of urinary extracellular vesicles in diabetic nephropathy. J Diabetes Res 2015:289734PubMedPubMedCentralGoogle Scholar
  51. 51.
    Barutta F, Tricarico M, Corbelli A, Annaratone L, Pinach S, Grimaldi S, Bruno G, Cimino D, Taverna D, Deregibus MC, Rastaldi MP, Perin PC, Gruden G (2013) Urinary exosomal microRNAs in incipient diabetic nephropathy. PLoS One 8:e73798PubMedPubMedCentralGoogle Scholar
  52. 52.
    Katome T, Namekata K, Mitamura Y, Semba K, Egawa M, Naito T, Harada C, Harada T (2015) Expression of intraocular peroxisome proliferator-activated receptor gamma in patients with proliferative diabetic retinopathy. J Diabetes Complicat 29:275–281PubMedGoogle Scholar
  53. 53.
    Tsukita S, Yamada T, Takahashi K, Munakata Y, Hosaka S, Takahashi H, Gao J, Shirai Y, Kodama S, Asai Y, Sugisawa T, Chiba Y, Kaneko K, Uno K, Sawada S, Imai J, Katagiri H (2017) MicroRNAs 106b and 222 improve hyperglycemia in a mouse model of insulin-deficient diabetes via pancreatic beta-cell proliferation. EBioMedicine 15:163–172PubMedGoogle Scholar
  54. 54.
    Kamalden TA, Macgregor-Das AM, Kannan SM, Dunkerly-Eyring B, Khaliddin N, Xu Z, Fusco AP, Yazib SA, Chow RC, Duh EJ, Halushka MK, Steenbergen C, Das S (2017) Exosomal MicroRNA-15a transfer from the pancreas augments diabetic complications by inducing oxidative stress. Antioxid Redox Signal 27:913–930PubMedCentralGoogle Scholar
  55. 55.
    Cianciaruso C, Phelps EA, Pasquier M, Hamelin R, Demurtas D, Alibashe Ahmed M, Piemonti L, Hirosue S, Swartz MA, De Palma M, Hubbell JA, Baekkeskov S (2017) Primary human and rat beta-cells release the intracellular autoantigens GAD65, IA-2, and proinsulin in exosomes together with cytokine-induced enhancers of immunity. Diabetes 66:460–473PubMedGoogle Scholar
  56. 56.
    Cai J, Han Y, Ren H, Chen C, He D, Zhou L, Eisner GM, Asico LD, Jose PA, Zeng C (2013) Extracellular vesicle-mediated transfer of donor genomic DNA to recipient cells is a novel mechanism for genetic influence between cells. J Mol Cell Biol 5:227–238PubMedPubMedCentralGoogle Scholar
  57. 57.
    Saari H, Lazaro-Ibanez E, Viitala T, Vuorimaa-Laukkanen E, Siljander P, Yliperttula M (2015) Microvesicle- and exosome-mediated drug delivery enhances the cytotoxicity of paclitaxel in autologous prostate cancer cells. J Control Release 220:727–737PubMedGoogle Scholar
  58. 58.
    Ohno S, Takanashi M, Sudo K, Ueda S, Ishikawa A, Matsuyama N, Fujita K, Mizutani T, Ohgi T, Ochiya T, Gotoh N, Kuroda M (2013) Systemically injected exosomes targeted to EGFR deliver antitumor microRNA to breast cancer cells. Mol Ther 21:185–191PubMedGoogle Scholar
  59. 59.
    Pashoutan Sarvar D, Shamsasenjan K, Akbarzadehlaleh P (2016) Mesenchymal stem cell-derived exosomes: new opportunity in cell-free therapy. Adv Pharm Bull 6:293–299PubMedPubMedCentralGoogle Scholar
  60. 60.
    Favaro E, Carpanetto A, Lamorte S, Fusco A, Caorsi C, Deregibus MC, Bruno S, Amoroso A, Giovarelli M, Porta M, Perin PC, Tetta C, Camussi G, Zanone MM (2014) Human mesenchymal stem cell-derived microvesicles modulate T cell response to islet antigen glutamic acid decarboxylase in patients with type 1 diabetes. Diabetologia 57:1664–1673PubMedGoogle Scholar
  61. 61.
    Favaro E, Carpanetto A, Caorsi C, Giovarelli M, Angelini C, Cavallo-Perin P, Tetta C, Camussi G, Zanone MM (2016) Human mesenchymal stem cells and derived extracellular vesicles induce regulatory dendritic cells in type 1 diabetic patients. Diabetologia 59:325–333PubMedGoogle Scholar
  62. 62.
    Cui C, Ye X, Chopp M, Venkat P, Zacharek A, Yan T, Ning R, Yu P, Cui G, Chen J (2016) miR-145 regulates diabetes-bone marrow stromal cell-induced Neurorestorative effects in diabetes stroke rats. Stem Cells Transl Med 5:1656–1667PubMedPubMedCentralGoogle Scholar
  63. 63.
    Wen D, Peng Y, Liu D, Weizmann Y, Mahato RI (2016) Mesenchymal stem cell and derived exosome as small RNA carrier and Immunomodulator to improve islet transplantation. J Control Release 238:166–175PubMedGoogle Scholar
  64. 64.
    Oh K, Kim SR, Kim DK, Seo MW, Lee C, Lee HM, Oh JE, Choi EY, Lee DS, Gho YS, Park KS (2015) In vivo differentiation of therapeutic insulin-producing cells from bone marrow cells via extracellular vesicle-mimetic Nanovesicles. ACS Nano 9:11718–11727PubMedGoogle Scholar
  65. 65.
    Zhao H, Shang Q, Pan Z, Bai Y, Li Z, Zhang H, Zhang Q, Guo C, Zhang L, Wang Q (2018) Exosomes from adipose-derived stem cells attenuate adipose inflammation and obesity through polarizing M2 macrophages and Beiging in white adipose tissue. Diabetes 67:235–247PubMedGoogle Scholar
  66. 66.
    Siegel RL, Miller KD, Jemal A (2016) Cancer statistics, 2016. CA Cancer J Clin 66:7–30PubMedPubMedCentralGoogle Scholar
  67. 67.
    Iacobuzio-Donahue CA (2012) Genetic evolution of pancreatic cancer: lessons learnt from the pancreatic cancer genome sequencing project. Gut 61:1085–1094PubMedGoogle Scholar
  68. 68.
    Yachida S, Jones S, Bozic I, Antal T, Leary R, Fu B, Kamiyama M, Hruban RH, Eshleman JR, Nowak MA, Velculescu VE, Kinzler KW, Vogelstein B, Iacobuzio-Donahue CA (2010) Distant metastasis occurs late during the genetic evolution of pancreatic cancer. Nature 467:1114–1117PubMedPubMedCentralGoogle Scholar
  69. 69.
    Falasca M, Kim M, Casari I (2016) Pancreatic cancer: current research and future directions. Biochim Biophys Acta 1865:123–132PubMedGoogle Scholar
  70. 70.
    Lou G, Song X, Yang F, Wu S, Wang J, Chen Z, Liu Y (2015) Exosomes derived from miR-122-modified adipose tissue-derived MSCs increase chemosensitivity of hepatocellular carcinoma. J Hematol Oncol 8:122PubMedPubMedCentralGoogle Scholar
  71. 71.
    Hong BS, Cho JH, Kim H, Choi EJ, Rho S, Kim J, Kim JH, Choi DS, Kim YK, Hwang D, Gho YS (2009) Colorectal cancer cell-derived microvesicles are enriched in cell cycle-related mRNAs that promote proliferation of endothelial cells. BMC Genomics 10:556PubMedPubMedCentralGoogle Scholar
  72. 72.
    Beloribi-Djefaflia S, Siret C, Lombardo D (2015) Exosomal lipids induce human pancreatic tumoral MiaPaCa-2 cells resistance through the CXCR4-SDF-1alpha signaling axis. Oncoscience 2:15–30PubMedGoogle Scholar
  73. 73.
    Takikawa T, Masamune A, Yoshida N, Hamada S, Kogure T, Shimosegawa T (2017) Exosomes derived from pancreatic stellate cells: MicroRNA signature and effects on pancreatic Cancer cells. Pancreas 46:19–27PubMedGoogle Scholar
  74. 74.
    Costa-Silva B, Aiello NM, Ocean AJ, Singh S, Zhang H, Thakur BK, Becker A, Hoshino A, Mark MT, Molina H, Xiang J, Zhang T, Theilen TM, Garcia-Santos G, Williams C, Ararso Y, Huang Y, Rodrigues G, Shen TL, Labori KJ, Lothe IM, Kure EH, Hernandez J, Doussot A, Ebbesen SH, Grandgenett PM, Hollingsworth MA, Jain M, Mallya K, Batra SK, Jarnagin WR, Schwartz RE, Matei I, Peinado H, Stanger BZ, Bromberg J, Lyden D (2015) Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver. Nat Cell Biol 17:816–826PubMedPubMedCentralGoogle Scholar
  75. 75.
    Liu Y, Gu Y, Cao X (2015) The exosomes in tumor immunity. Oncoimmunology 4:e1027472PubMedPubMedCentralGoogle Scholar
  76. 76.
    Amedei A, Niccolai E, Prisco D (2014) Pancreatic cancer: role of the immune system in cancer progression and vaccine-based immunotherapy. Hum Vaccin Immunother 10:3354–3368PubMedCentralGoogle Scholar
  77. 77.
    Hori SI, Herrera A, Rossi JJ, Zhou J (2018) Current advances in aptamers for Cancer diagnosis and therapy. Cancer 10(1):E9Google Scholar
  78. 78.
    Janssen LME, Ramsay EE, Logsdon CD, Overwijk WW (2017) The immune system in cancer metastasis: friend or foe? J Immunother Cancer 5:79PubMedPubMedCentralGoogle Scholar
  79. 79.
    Ding G, Zhou L, Qian Y, Fu M, Chen J, Chen J, Xiang J, Wu Z, Jiang G, Cao L (2015) Pancreatic cancer-derived exosomes transfer miRNAs to dendritic cells and inhibit RFXAP expression via miR-212-3p. Oncotarget 6:29877–29888PubMedPubMedCentralGoogle Scholar
  80. 80.
    Kamisawa T, Wood LD, Itoi T, Takaori K (2016) Pancreatic cancer. Lancet (London, England) 388:73–85Google Scholar
  81. 81.
    Sagar G, Sah RP, Javeed N, Dutta SK, Smyrk TC, Lau JS, Giorgadze N, Tchkonia T, Kirkland JL, Chari ST, Mukhopadhyay D (2016) Pathogenesis of pancreatic cancer exosome-induced lipolysis in adipose tissue. Gut 65:1165–1174PubMedGoogle Scholar
  82. 82.
    Javeed N, Sagar G, Dutta SK, Smyrk TC, Lau JS, Bhattacharya S, Truty M, Petersen GM, Kaufman RJ, Chari ST, Mukhopadhyay D (2015) Pancreatic cancer-derived exosomes cause paraneoplastic beta-cell dysfunction. Clin Cancer Res 21:1722–1733PubMedGoogle Scholar
  83. 83.
    Patel GK, Patton MC, Singh S, Khushman M, Singh AP (2016) Pancreatic cancer exosomes: shedding off for a meaningful journey. Pancreat Disord Ther 6:e148PubMedPubMedCentralGoogle Scholar
  84. 84.
    Oettle H, Post S, Neuhaus P, Gellert K, Langrehr J, Ridwelski K, Schramm H, Fahlke J, Zuelke C, Burkart C, Gutberlet K, Kettner E, Schmalenberg H, Weigang-Koehler K, Bechstein WO, Niedergethmann M, Schmidt-Wolf I, Roll L, Doerken B, Riess H (2007) Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA 297:267–277PubMedPubMedCentralGoogle Scholar
  85. 85.
    Corcoran C, Rani S, O’Brien K, O’Neill A, Prencipe M, Sheikh R, Webb G, McDermott R, Watson W, Crown J, O’Driscoll L (2012) Docetaxel-resistance in prostate cancer: evaluating associated phenotypic changes and potential for resistance transfer via exosomes. PLoS One 7:e50999PubMedPubMedCentralGoogle Scholar
  86. 86.
    Wei Y, Lai X, Yu S, Chen S, Ma Y, Zhang Y, Li H, Zhu X, Yao L, Zhang J (2014) Exosomal miR-221/222 enhances tamoxifen resistance in recipient ER-positive breast cancer cells. Breast Cancer Res Treat 147:423–431PubMedGoogle Scholar
  87. 87.
    Yu S, Cao H, Shen B, Feng J (2015) Tumor-derived exosomes in cancer progression and treatment failure. Oncotarget 6:37151–37168PubMedPubMedCentralGoogle Scholar
  88. 88.
    Richards KE, Zeleniak AE, Fishel ML, Wu J, Littlepage LE, Hill R (2017) Cancer-associated fibroblast exosomes regulate survival and proliferation of pancreatic cancer cells. Oncogene 36:1770–1778PubMedGoogle Scholar
  89. 89.
    Nonaka T, Wong DTW (2017) Saliva-Exosomics in Cancer: molecular characterization of cancer-derived exosomes in saliva. Enzyme 42:125–151Google Scholar
  90. 90.
    Huang T, Deng CX (2019) Current progresses of exosomes as cancer diagnostic and prognostic biomarkers. Int J Biol Sci 15:1–11PubMedPubMedCentralGoogle Scholar
  91. 91.
    Paoli D, Pecora G, Pallotti F, Faja F, Pelloni M, Lenzi A, Lombardo F (2019) Cytological and molecular aspects of the ageing sperm. Hum Reprod (Oxford, England) 34:218–227Google Scholar
  92. 92.
    Sun Z, Shi K, Yang S, Liu J, Zhou Q, Wang G, Song J, Li Z, Zhang Z, Yuan W (2018) Effect of exosomal miRNA on cancer biology and clinical applications. Mol Cancer 17:147PubMedPubMedCentralGoogle Scholar
  93. 93.
    Li LM, Liu H, Liu XH, Hu HB, Liu SM (2019) Clinical significance of exosomal miRNAs and proteins in three human cancers with high mortality in China. Oncol Lett 17:11–22PubMedGoogle Scholar
  94. 94.
    Lu L, Risch HA (2016) Exosomes: potential for early detection in pancreatic cancer. Future Oncol (London, England) 12:1081–1090Google Scholar
  95. 95.
    Joshi GK, Deitz-McElyea S, Liyanage T, Lawrence K, Mali S, Sardar R, Korc M (2015) Label-free Nanoplasmonic-based short noncoding RNA sensing at attomolar concentrations allows for quantitative and highly specific assay of MicroRNA-10b in biological fluids and circulating exosomes. ACS Nano 9:11075–11089PubMedPubMedCentralGoogle Scholar
  96. 96.
    Madhavan B, Yue S, Galli U, Rana S, Gross W, Muller M, Giese NA, Kalthoff H, Becker T, Buchler MW, Zoller M (2015) Combined evaluation of a panel of protein and miRNA serum-exosome biomarkers for pancreatic cancer diagnosis increases sensitivity and specificity. Int J Cancer 136:2616–2627PubMedGoogle Scholar
  97. 97.
    Herreros-Villanueva M, Bujanda L (2016) Glypican-1 in exosomes as biomarker for early detection of pancreatic cancer. Ann Transl Med 4:64PubMedPubMedCentralGoogle Scholar
  98. 98.
    Lucien F, Lac V, Billadeau DD, Borgida A, Gallinger S, Leong HS (2019) Glypican-1 and glycoprotein 2 bearing extracellular vesicles do not discern pancreatic cancer from benign pancreatic diseases. Oncotarget 10:1045–1055PubMedPubMedCentralGoogle Scholar
  99. 99.
    Hoshino A, Costa-Silva B, Shen TL, Rodrigues G, Hashimoto A, Mark MT, Molina H, Kohsaka S, Di Giannatale A, Ceder S, Singh S, Williams C, Soplop N, Uryu K, Pharmer L, King T, Bojmar L, Davies AE, Ararso Y, Zhang T, Zhang H, Hernandez J, Weiss JM, Dumont-Cole VD, Kramer K, Wexler LH, Narendran A, Schwartz GK, Healey JH, Sandstrom P, Labori KJ, Kure EH, Grandgenett PM, Hollingsworth MA, de Sousa M, Kaur S, Jain M, Mallya K, Batra SK, Jarnagin WR, Brady MS, Fodstad O, Muller V, Pantel K, Minn AJ, Bissell MJ, Garcia BA, Kang Y, Rajasekhar VK, Ghajar CM, Matei I, Peinado H, Bromberg J, Lyden D (2015) Tumour exosome integrins determine organotropic metastasis. Nature 527:329–335PubMedPubMedCentralGoogle Scholar
  100. 100.
    Moutinho-Ribeiro P, Macedo G, Melo SA (2018) Pancreatic cancer diagnosis and management: has the time come to prick the bubble? Front Endocrinol 9:779Google Scholar
  101. 101.
    Nuzhat Z, Kinhal V, Sharma S, Rice GE, Joshi V, Salomon C (2017) Tumour-derived exosomes as a signature of pancreatic cancer - liquid biopsies as indicators of tumour progression. Oncotarget 8:17279–17291PubMedGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Cancer Biology Lab, Department of Biochemistry and Bioinformatics, GISGITAM (Deemed to be University)VisakhapatnamIndia
  2. 2.Department of Biochemistry and Bioinformatics, GISGITAM (Deemed to be University)VisakhapatnamIndia

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