Research progress on exosomes in the early diagnosis and treatment of non-small cell lung cancer_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

MA Jun , WU Bin , ZHANG Guozhong ,  SHI Hongcan

Department of General Thoracic Surgery, Medical College of Yangzhou University, Yangzhou, 225001, Jiangsu, P.R.China;

Corresponding author：

SHI Hongcan, Email: shihongcan@hotmail.com

Keywords：

Exosome; non-small cell lung cancer; early diagnosis; treatment

DOI：

10.7507/1007-4848.201810020

Video：

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Lung cancer is one of the most common malignant tumors in the world, and also one of the most common malignant tumors with the highest incidence, highest mortality, the fastest growth rate and the worst prognosis. Therefore, a deeper understanding of the disease is urgently needed in order to establish new diagnostic and therapeutic approaches. Exosomes, a kind of extracellular vesicles secreted by cells, can deliver various bioactive molecules, such as proteins, mRNA, mircoRNA, lipids, etc, and their potential value in the diagnosis, treatment and prognosis of lung cancer has been supported by a large number of literatures. In this review, we reviewed the role of exosomes in the of development, early diagnosis, treatment and prognosis of non-small cell lung cancer.

1.	Siegel RL, Miller KD, Fedewa SA, et al. Colorectal cancer statistics, 2017. CA Cancer J Clin, 2017, 67(3): 177-193.
2.	Yang Q, Diamond MP, Al-Hendy A. The emerging role of extracellular vesicle-derived miRNAs: implication in cancer progression and stem cell related diseases. J Clin Epigenet, 2016, 2(1): pii: 13.
3.	Munson P, Shukla A. Exosomes: Potential in cancer diagnosis and therapy. Medicines (Basel), 2015, 2(4): 310-327.
4.	Johnstone RM, Adam M, Hammond JR, et al. Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes). J Biol Chem, 1987, 262(19): 9412-9420.
5.	Taverna S, Giallombardo M, Gil-Bazo I, et al. Exosomes isolation and characterization in serum is feasible in non-small cell lung cancer patients: critical analysis of evidence and potential role in clinical practice. Oncotarget, 2016, 7(19): 28748-28760.
6.	Ventimiglia LN, Alonso MA. Biogenesis and function of T cell-derived exosomes. Front Cell Dev Biol, 2016, 4: 84.
7.	Van Niel G, Mallegol J, Bevilacqua C, et al. Intestinal epithelial exosomes carry MHC class Ⅱ/peptides able to inform the immune system in mice. Gut, 2003, 52(12): 1690-1697.
8.	Théry C, Zitvogel L, Amigorena S. Exosomes: composition, biogenesis and function. Nat Rev Immunol, 2002, 2(8): 569-579.
9.	Mathivanan S, Simpson RJ. ExoCarta: A compendium of exosomal proteins and RNA. Proteomics, 2009, 9(21): 4997-5000.
10.	Valadi H, Ekström K, Bossios A, et al. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol, 2007, 9(6): 654-659.
11.	Frediani JN, Fabbri M. Essential role of miRNAs in orchestrating the biology of the tumor microenvironment. Mol Cancer, 2016, 15(1): 42.
12.	Cui H, Seubert B, Stahl E, et al. Tissue inhibitor of metalloproteinases-1 induces a pro-tumourigenic increase of miR-210 in lung adenocarcinoma cells and their exosomes. Oncogene, 2015, 34(28): 3640-3650.
13.	Hsu YL, Hung JY, Chang WA, et al. Hypoxic lung cancer-secreted exosomal miR-23a increased angiogenesis and vascular permeability by targeting prolyl hydroxylase and tight junction protein ZO-1. Oncogene, 2017, 36(34): 4929-4942.
14.	Rahman MA, Barger JF, Lovat F, et al. Lung cancer exosomes as drivers of epithelial mesenchymal transition. Oncotarget, 2016, 7(34): 54852-54866.
15.	Berchem G, Noman MZ, Bosseler M, et al. Hypoxic tumor-derived microvesicles negatively regulate NK cell function by a mechanism involving TGF-β and miR23a transfer. Oncoimmunology, 2015, 5(4): e1062968.
16.	万双双, 蔡志坚. 外泌体在肿瘤生物治疗中的研究进展. 中国肿瘤生物治疗杂志, 2016, 23(4): 571-574.
17.	Wang Y, Yi J, Chen X, et al. The regulation of cancer cell migration by lung cancer cell-derived exosomes through TGF-β and IL-10. Oncol Lett, 2016, 11(2): 1527-1530.
18.	Cai Z, Yang F, Yu L, et al. Activated T cell exosomes promote tumor invasion via Fas signaling pathway. J Immunol, 2012, 188(12): 5954-5961.
19.	Li J, Yu J, Zhang H, et al. Exosomes-derived MiR-302b suppresses lung cancer cell proliferation and migration via TGFβRⅡ inhibition. Cell Physiol Biochem, 2016, 38(5): 1715-1726.
20.	Chen X, Ba Y, Ma L, et al. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res, 2008, 18(10): 997-1006.
21.	Rabinowits G, Gerçel-Taylor C, Day JM, et al. Exosomal microRNA: a diagnostic marker for lung cancer. Clin Lung Cancer, 2009, 10(1): 42-46.
22.	Cazzoli R, Buttitta F, Di Nicola M, et al. microRNAs derived from circulating exosomes as noninvasive biomarkers for screening and diagnosing lung cancer. J Thorac Oncol, 2013, 8(9): 1156-1162.
23.	Huang SH, Li Y, Zhang J, et al. Epidermal growth factor receptor-containing exosomes induce tumor-specific regulatory T cells. Cancer Invest, 2013, 31(5): 330-335.
24.	Park JO, Choi DY, Choi DS, et al. Identification and characterization of proteins isolated from microvesicles derived from human lung cancer pleural effusions. Proteomics, 2013, 13(14): 2125-2134.
25.	Sandfeld-Paulsen B, Jakobsen KR, Bæk R, et al. Exosomal proteins as diagnostic biomarkers in lung cancer. J Thorac Oncol, 2016, 11(10): 1701-1710.
26.	Clark DJ, Fondrie WE, Yang A, et al. Triple SILAC quantitative proteomic analysis reveals differential abundance of cell signaling proteins between normal and lung cancer-derived exosomes. J Proteomics, 2016, 133: 161-169.
27.	Li W, Hu Y, Jiang T, et al. Rab27A regulates exosome secretion from lung adenocarcinoma cells A549: involvement of EPI64. APMIS, 2014, 122(11): 1080-1087.
28.	Romagnoli GG, Zelante BB, Toniolo PA, et al. Dendritic cell-derived exosomes may be a tool for cancer immunotherapy by converting tumor cells into immunogenic targets. Front Immunol, 2015, 5: 692.
29.	Besse B, Charrier M, Lapierre V, et al. Dendritic cell-derived exosomes as maintenance immunotherapy after first line chemotherapy in NSCLC. Oncoimmunology, 2015, 5(4): e1071008.
30.	Srivastava A, Amreddy N, Babu A, et al. Nanosomes carrying doxorubicin exhibit potent anticancer activity against human lung cancer cells. Sci Rep, 2016, 6: 38541.
31.	Kim MS, Haney MJ, Zhao Y, et al. Development of exosome-encapsulated paclitaxel to overcome MDR in cancer cells. Nanomedicine, 2016, 12(3): 655-664.
32.	Aqil F, Kausar H, Agrawal AK, et al. Exosomal formulation enhances therapeutic response of celastrol against lung cancer. Exp Mol Pathol, 2016, 101(1): 12-21.
33.	Dejima H, Iinuma H, Kanaoka R, et al. Exosomal microRNA in plasma as a non-invasive biomarker for the recurrence of non-small cell lung cancer. Oncol Lett, 2017, 13(3): 1256-1263.
34.	Yuwen DL, Sheng BB, Liu J, et al. MiR-146a-5p level in serum exosomes predicts therapeutic effect of cisplatin in non-small cell lung cancer. Eur Rev Med Pharmacol Sci, 2017, 21(11): 2650-2658.
35.	Sandfeld-Paulsen B, Aggerholm-Pedersen N, Bæk R, et al. Exosomal proteins as prognostic biomarkers in non-small cell lung cancer. Mol Oncol, 2016, 10(10): 1595-1602.
36.	Silva J, García V, Zaballos Á, et al. Vesicle-related microRNAs in plasma of nonsmall cell lung cancer patients and correlation with survival. Eur Respir J, 2011, 37(3): 617-623.

1. Siegel RL, Miller KD, Fedewa SA, et al. Colorectal cancer statistics, 2017. CA Cancer J Clin, 2017, 67(3): 177-193.
2. Yang Q, Diamond MP, Al-Hendy A. The emerging role of extracellular vesicle-derived miRNAs: implication in cancer progression and stem cell related diseases. J Clin Epigenet, 2016, 2(1): pii: 13.
3. Munson P, Shukla A. Exosomes: Potential in cancer diagnosis and therapy. Medicines (Basel), 2015, 2(4): 310-327.
4. Johnstone RM, Adam M, Hammond JR, et al. Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes). J Biol Chem, 1987, 262(19): 9412-9420.
5. Taverna S, Giallombardo M, Gil-Bazo I, et al. Exosomes isolation and characterization in serum is feasible in non-small cell lung cancer patients: critical analysis of evidence and potential role in clinical practice. Oncotarget, 2016, 7(19): 28748-28760.
6. Ventimiglia LN, Alonso MA. Biogenesis and function of T cell-derived exosomes. Front Cell Dev Biol, 2016, 4: 84.
7. Van Niel G, Mallegol J, Bevilacqua C, et al. Intestinal epithelial exosomes carry MHC class Ⅱ/peptides able to inform the immune system in mice. Gut, 2003, 52(12): 1690-1697.
8. Théry C, Zitvogel L, Amigorena S. Exosomes: composition, biogenesis and function. Nat Rev Immunol, 2002, 2(8): 569-579.
9. Mathivanan S, Simpson RJ. ExoCarta: A compendium of exosomal proteins and RNA. Proteomics, 2009, 9(21): 4997-5000.
10. Valadi H, Ekström K, Bossios A, et al. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol, 2007, 9(6): 654-659.
11. Frediani JN, Fabbri M. Essential role of miRNAs in orchestrating the biology of the tumor microenvironment. Mol Cancer, 2016, 15(1): 42.
12. Cui H, Seubert B, Stahl E, et al. Tissue inhibitor of metalloproteinases-1 induces a pro-tumourigenic increase of miR-210 in lung adenocarcinoma cells and their exosomes. Oncogene, 2015, 34(28): 3640-3650.
13. Hsu YL, Hung JY, Chang WA, et al. Hypoxic lung cancer-secreted exosomal miR-23a increased angiogenesis and vascular permeability by targeting prolyl hydroxylase and tight junction protein ZO-1. Oncogene, 2017, 36(34): 4929-4942.
14. Rahman MA, Barger JF, Lovat F, et al. Lung cancer exosomes as drivers of epithelial mesenchymal transition. Oncotarget, 2016, 7(34): 54852-54866.
15. Berchem G, Noman MZ, Bosseler M, et al. Hypoxic tumor-derived microvesicles negatively regulate NK cell function by a mechanism involving TGF-β and miR23a transfer. Oncoimmunology, 2015, 5(4): e1062968.
16. 万双双, 蔡志坚. 外泌体在肿瘤生物治疗中的研究进展. 中国肿瘤生物治疗杂志, 2016, 23(4): 571-574.
17. Wang Y, Yi J, Chen X, et al. The regulation of cancer cell migration by lung cancer cell-derived exosomes through TGF-β and IL-10. Oncol Lett, 2016, 11(2): 1527-1530.
18. Cai Z, Yang F, Yu L, et al. Activated T cell exosomes promote tumor invasion via Fas signaling pathway. J Immunol, 2012, 188(12): 5954-5961.
19. Li J, Yu J, Zhang H, et al. Exosomes-derived MiR-302b suppresses lung cancer cell proliferation and migration via TGFβRⅡ inhibition. Cell Physiol Biochem, 2016, 38(5): 1715-1726.
20. Chen X, Ba Y, Ma L, et al. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res, 2008, 18(10): 997-1006.
21. Rabinowits G, Gerçel-Taylor C, Day JM, et al. Exosomal microRNA: a diagnostic marker for lung cancer. Clin Lung Cancer, 2009, 10(1): 42-46.
22. Cazzoli R, Buttitta F, Di Nicola M, et al. microRNAs derived from circulating exosomes as noninvasive biomarkers for screening and diagnosing lung cancer. J Thorac Oncol, 2013, 8(9): 1156-1162.
23. Huang SH, Li Y, Zhang J, et al. Epidermal growth factor receptor-containing exosomes induce tumor-specific regulatory T cells. Cancer Invest, 2013, 31(5): 330-335.
24. Park JO, Choi DY, Choi DS, et al. Identification and characterization of proteins isolated from microvesicles derived from human lung cancer pleural effusions. Proteomics, 2013, 13(14): 2125-2134.
25. Sandfeld-Paulsen B, Jakobsen KR, Bæk R, et al. Exosomal proteins as diagnostic biomarkers in lung cancer. J Thorac Oncol, 2016, 11(10): 1701-1710.
26. Clark DJ, Fondrie WE, Yang A, et al. Triple SILAC quantitative proteomic analysis reveals differential abundance of cell signaling proteins between normal and lung cancer-derived exosomes. J Proteomics, 2016, 133: 161-169.
27. Li W, Hu Y, Jiang T, et al. Rab27A regulates exosome secretion from lung adenocarcinoma cells A549: involvement of EPI64. APMIS, 2014, 122(11): 1080-1087.
28. Romagnoli GG, Zelante BB, Toniolo PA, et al. Dendritic cell-derived exosomes may be a tool for cancer immunotherapy by converting tumor cells into immunogenic targets. Front Immunol, 2015, 5: 692.
29. Besse B, Charrier M, Lapierre V, et al. Dendritic cell-derived exosomes as maintenance immunotherapy after first line chemotherapy in NSCLC. Oncoimmunology, 2015, 5(4): e1071008.
30. Srivastava A, Amreddy N, Babu A, et al. Nanosomes carrying doxorubicin exhibit potent anticancer activity against human lung cancer cells. Sci Rep, 2016, 6: 38541.
31. Kim MS, Haney MJ, Zhao Y, et al. Development of exosome-encapsulated paclitaxel to overcome MDR in cancer cells. Nanomedicine, 2016, 12(3): 655-664.
32. Aqil F, Kausar H, Agrawal AK, et al. Exosomal formulation enhances therapeutic response of celastrol against lung cancer. Exp Mol Pathol, 2016, 101(1): 12-21.
33. Dejima H, Iinuma H, Kanaoka R, et al. Exosomal microRNA in plasma as a non-invasive biomarker for the recurrence of non-small cell lung cancer. Oncol Lett, 2017, 13(3): 1256-1263.
34. Yuwen DL, Sheng BB, Liu J, et al. MiR-146a-5p level in serum exosomes predicts therapeutic effect of cisplatin in non-small cell lung cancer. Eur Rev Med Pharmacol Sci, 2017, 21(11): 2650-2658.
35. Sandfeld-Paulsen B, Aggerholm-Pedersen N, Bæk R, et al. Exosomal proteins as prognostic biomarkers in non-small cell lung cancer. Mol Oncol, 2016, 10(10): 1595-1602.
36. Silva J, García V, Zaballos Á, et al. Vesicle-related microRNAs in plasma of nonsmall cell lung cancer patients and correlation with survival. Eur Respir J, 2011, 37(3): 617-623.

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