Effects of Exosomal Viral Components on the Tumor Microenvironment
Abstract
:Simple Summary
Abstract
1. Introduction
2. Overview of Exosomes
2.1. Exosome Formation and Composition
2.2. Isolation and Biological Characterization of Exosomes
3. Exosomes and Viruses
4. Effect of Exosomal Viral Components on the Tumor Microenvironment
4.1. EBV-Related Cancers
4.2. HPV-Related Cancers
4.3. Hepatitis Virus-Related Cancers
4.4. HIV-Related Cancers
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Cao, W.; Chen, H.-D.; Yu, Y.-W.; Li, N.; Chen, W.-Q. Changing profiles of cancer burden worldwide and in China: A secondary analysis of the global cancer statistics. Chin. Med. J. 2021, 134, 783–791. [Google Scholar] [CrossRef] [PubMed]
- Hui, L.; Chen, Y. Tumor microenvironment: Sanctuary of the devil. Cancer Lett. 2015, 368, 7–13. [Google Scholar] [CrossRef] [PubMed]
- Hinshaw, D.C.; Shevde, L.A. The tumor microenvironment innately modulates cancer progression. Cancer Res. 2019, 79, 4557–4566. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hernández-Camarero, P.; López-Ruiz, E.; Marchal, J.A.; Perán, M. Cancer: A mirrored room between tumor bulk and tumor microenvironment. J. Exp. Clin. Cancer Res. 2021, 40, 217. [Google Scholar] [CrossRef] [PubMed]
- Zaborowski, M.P.; Balaj, L.; Breakefield, X.O.; Lai, C.P. Extracellular Vesicles: Composition, Biological Relevance, and Methods of Study. Bioscience 2015, 65, 783–797. [Google Scholar] [CrossRef] [Green Version]
- Yáñez-Mó, M.; Siljander, P.R.-M.; Andreu, Z.; Bedina Zavec, A.; Borràs, F.E.; Buzas, E.I.; Buzas, K.; Casal, E.; Cappello, F.; Carvalho, J.; et al. Biological properties of extracellular vesicles and their physiological functions. J. Extracell. Vesicles 2015, 4, 27066. [Google Scholar] [CrossRef] [Green Version]
- Théry, C.; Witwer, K.W.; Aikawa, E.; Alcaraz, M.J.; Anderson, J.D.; Andriantsitohaina, R.; Antoniou, A.; Arab, T.; Archer, F.; Atkin-Smith, G.K.; et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): A position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J. Extracell. Vesicles 2018, 7, 1535750. [Google Scholar] [CrossRef] [Green Version]
- Théry, C.; Zitvogel, L.; Amigorena, S. Exosomes: Composition, biogenesis and function. Nat. Rev. Immunol. 2002, 2, 569–579. [Google Scholar] [CrossRef]
- Zhang, C.; Ji, Q.; Yang, Y.; Li, Q.; Wang, Z. Exosome: Function and Role in Cancer Metastasis and Drug Resistance. Technol. Cancer Res. Treat. 2018, 17, 1533033818763450. [Google Scholar] [CrossRef] [Green Version]
- Zhang, L.; Yu, D. Exosomes in cancer development, metastasis, and immunity. Biochim. Biophys. Acta (BBA) Rev. Cancer 2019, 1871, 455–468. [Google Scholar] [CrossRef]
- Miller, I.V.; Grünewald, T.G.P. Tumour-derived exosomes: Tiny envelopes for big stories. Biol. Cell 2015, 107, 287–305. [Google Scholar] [CrossRef] [PubMed]
- Johnstone, R.M.; Adam, M.; Hammond, J.R.; Orr, L.; Turbide, C. Vesicle formation during reticulocyte maturation. Associa-tion of plasma membrane activities with released vesicles (exosomes). J. Biol. Chem. 1987, 262, 9412–9420. [Google Scholar] [CrossRef]
- Whitford, W.; Guterstam, P. Exosome manufacturing status. Future Med. Chem. 2019, 11, 1225–1236. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Xu, R.; Greening, D.W.; Zhu, H.-J.; Takahashi, N.; Simpson, R.J. Extracellular vesicle isolation and characterization: Toward clinical application. J. Clin. Investig. 2016, 126, 1152–1162. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Valadi, H.; Ekström, K.; Bossios, A.; Sjöstrand, M.; Lee, J.J.; Lötvall, J.O. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat. Cell Biol. 2007, 9, 654–659. [Google Scholar] [CrossRef] [Green Version]
- Zhang, X.; Xu, D.; Song, Y.; He, R.; Wang, T. Research Progress in the Application of Exosomes in Immunotherapy. Front. Immunol. 2022, 13, 731516. [Google Scholar] [CrossRef]
- Simpson, R.J.; Jensen, S.S.; Lim, J.W.E. Proteomic profiling of exosomes: Current perspectives. Proteomics 2008, 8, 4083–4099. [Google Scholar] [CrossRef]
- Simons, M.; Raposo, G. Exosomes—Vesicular carriers for intercellular communication. Curr. Opin. Cell Biol. 2009, 21, 575–581. [Google Scholar] [CrossRef]
- Rashed, M.H.; Bayraktar, E.; Helal, G.K.; Abd-Ellah, M.F.; Amero, P.; Chavez-Reyes, A.; Rodriguez-Aguayo, C. Exosomes: From Garbage Bins to Promising Therapeutic Targets. Int. J. Mol. Sci. 2017, 18, 538. [Google Scholar] [CrossRef] [Green Version]
- Kalluri, R.; LeBleu, V.S. The biology, function, and biomedical applications of exosomes. Science 2020, 367, eaau6977. [Google Scholar] [CrossRef]
- Tian, X.; Shen, H.; Li, Z.; Wang, T.; Wang, S. Tumor-derived exosomes, myeloid-derived suppressor cells, and tumor microenvironment. J. Hematol. Oncol. 2019, 12, 84. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Doyle, L.; Wang, M. Overview of Extracellular Vesicles, Their Origin, Composition, Purpose, and Methods for Exosome Isolation and Analysis. Cells 2019, 8, 727. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gurunathan, S.; Kang, M.-H.; Jeyaraj, M.; Qasim, M.; Kim, J.-H. Review of the Isolation, Characterization, Biological Function, and Multifarious Therapeutic Approaches of Exosomes. Cells 2019, 8, 307. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, Y.; Bi, J.; Huang, J.; Tang, Y.; Du, S.; Li, P. Exosome: A Review of Its Classification, Isolation Techniques, Storage, Diagnostic and Targeted Therapy Applications. Int. J. Nanomed. 2020, 15, 6917–6934. [Google Scholar] [CrossRef] [PubMed]
- Zhu, L.; Sun, H.-T.; Wang, S.; Huang, S.-L.; Zheng, Y.; Wang, C.-Q.; Hu, B.-Y.; Qin, W.; Zou, T.-T.; Fu, Y.; et al. Isolation and characterization of exosomes for cancer research. J. Hematol. Oncol. 2020, 13, 152. [Google Scholar] [CrossRef] [PubMed]
- Zhou, C.; Tan, L.; Ding, C. Advances of RNA virus increasing viral infection through the exosomes. Microbiol. China 2017, 44, 2988–2996. [Google Scholar]
- Khan, G.; Ahmed, W. Isolation and Characterization of Exosomes Released by EBV-Immortalized Cells. Methods Mol. Biol. 2016, 1532, 147–158. [Google Scholar] [CrossRef]
- Wu, J.; Yang, J.; Ding, J.; Guo, X.; Zhu, X.-Q.; Zheng, Y. Exosomes in virus-associated cancer. Cancer Lett. 2018, 438, 44–51. [Google Scholar] [CrossRef]
- Burd, E.M. Human Papillomavirus and Cervical Cancer. Clin. Microbiol. Rev. 2003, 16, 889–899. [Google Scholar] [CrossRef] [Green Version]
- Tsao, S.W.; Tsang, C.M.; Lo, K.W. Epstein–Barr virus infection and nasopharyngeal carcinoma. Philos. Trans. R. Soc. B Biol. Sci. 2017, 372, 20160270. [Google Scholar] [CrossRef]
- Thompson, M.P.; Kurzrock, R. Epstein-Barr Virus and Cancer. Clin. Cancer Res. 2004, 10, 803–821. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Morales-Sánchez, A.; Fuentes-Pananá, E.M. Human Viruses and Cancer. Viruses 2014, 6, 4047–4079. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hu, C.; Chen, M.; Jiang, R.; Guo, Y.; Wu, M.; Zhang, X. Exosome-related tumor microenvironment. J. Cancer 2018, 9, 3084–3092. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Longatti, A. The Dual Role of Exosomes in Hepatitis A and C Virus Transmission and Viral Immune Activation. Viruses 2015, 7, 6707–6715. [Google Scholar] [CrossRef] [Green Version]
- Li, S.; Li, S.; Wu, S.; Chen, L. Exosomes Modulate the Viral Replication and Host Immune Responses in HBV Infection. BioMed Res. Int. 2019, 2019, 2103943. [Google Scholar] [CrossRef] [Green Version]
- Masciopinto, F.; Giovani, C.; Campagnoli, S.; Galli-Stampino, L.; Colombatto, P.; Brunetto, M.; Yen, T.S.B.; Houghton, M.; Pileri, P.; Abrignani, S. Association of hepatitis C virus envelope proteins with exosomes. Eur. J. Immunol. 2004, 34, 2834–2842. [Google Scholar] [CrossRef]
- Conigliaro, A.; Costa, V.; Dico, A.L.; Saieva, L.; Buccheri, S.; Dieli, F.; Manno, M.; Raccosta, S.; Mancone, C.; Tripodi, M.; et al. CD90+ liver cancer cells modulate endothelial cell phenotype through the release of exosomes containing H19 lncRNA. Mol. Cancer 2015, 14, 155. [Google Scholar] [CrossRef]
- Kogure, T.; Lin, W.-L.; Yan, I.K.; Braconi, C.; Patel, T. Intercellular nanovesicle-mediated microRNA transfer: A mechanism of environmental modulation of hepatocellular cancer cell growth. Hepatology 2011, 54, 1237–1248. [Google Scholar] [CrossRef] [Green Version]
- Pegtel, D.M.; Cosmopoulos, K.; Thorley-Lawson, D.A.; van Eijndhoven, M.A.J.; Hopmans, E.S.; Lindenberg, J.L.; de Gruijl, T.D.; Würdinger, T.; Middeldorp, J.M. Functional delivery of viral miRNAs via exosomes. Proc. Natl. Acad. Sci. USA 2010, 107, 6328–6333. [Google Scholar] [CrossRef] [Green Version]
- Choi, H.; Lee, H.; Kim, S.R.; Gho, Y.S.; Lee, S.K. Epstein-Barr Virus-Encoded MicroRNA BART15-3p Promotes Cell Apoptosis Partially by Targeting BRUCE. J. Virol. 2013, 87, 8135–8144. [Google Scholar] [CrossRef] [Green Version]
- Ceccarelli, S.; Visco, V.; Raffa, S.; Wakisaka, N.; Pagano, J.S.; Torrisi, M.R. Epstein-Barr virus latent membrane protein 1 promotes concentration in multivesicular bodies of fibroblast growth factor 2 and its release through exosomes. Int. J. Cancer 2007, 121, 1494–1506. [Google Scholar] [CrossRef] [PubMed]
- Shao, H.; Chung, J.; Issadore, D. Diagnostic technologies for circulating tumour cells and exosomes. Biosci. Rep. 2016, 36, e00292. [Google Scholar] [CrossRef] [PubMed]
- Plummer, M.; de Martel, C.; Vignat, J.; Ferlay, J.; Bray, F.; Franceschi, S. Global burden of cancers attributable to infections in 2012: A synthetic analysis. Lancet Glob. Health 2016, 4, e609–e616. [Google Scholar] [CrossRef] [Green Version]
- de Martel, C.; Georges, D.; Bray, F.; Ferlay, J.; Clifford, G.M. Global burden of cancer attributable to infections in 2018: A worldwide incidence analysis. Lancet Glob. Health 2020, 8, e180–e190. [Google Scholar] [CrossRef] [Green Version]
- Thomas, E.; Thankan, R.S.; Purushottamachar, P.; Huang, W.; Kane, M.A.; Zhang, Y.; Ambulos, N.; Weber, D.J.; Njar, V.C.O. Transcriptome profiling reveals that VNPP433-3β, the lead next-generation galeterone analog inhibits prostate cancer stem cells by downregulating epithelial–mesenchymal transition and stem cell markers. Mol. Carcinog. 2022, 61, 643–654. [Google Scholar] [CrossRef]
- Tu, S.-M. Stem Cell Theory of Cancer: Implications of a Viral Etiology in Certain Malignancies. Cancers 2021, 13, 2738. [Google Scholar] [CrossRef]
- Yasui, M.; Kunita, A.; Numakura, S.; Uozaki, H.; Ushiku, T.; Fukayama, M. Cancer stem cells in Epstein-Barr virus-associated gastric carcinoma. Cancer Sci. 2020, 111, 2598–2607. [Google Scholar] [CrossRef]
- Kong, Q.-L.; Hu, L.-J.; Cao, J.-Y.; Huang, Y.-J.; Xu, L.-H.; Liang, Y.; Xiong, D.; Guan, S.; Guo, B.-H.; Mai, H.-Q.; et al. Epstein-Barr Virus-Encoded LMP2A Induces an Epithelial–Mesenchymal Transition and Increases the Number of Side Population Stem-like Cancer Cells in Nasopharyngeal Carcinoma. PLoS Pathog. 2010, 6, e1000940. [Google Scholar] [CrossRef]
- Tan, S.; Xia, L.; Yi, P.; Han, Y.; Tang, L.; Pan, Q.; Tian, Y.; Rao, S.; Oyang, L.; Liang, J.; et al. Exosomal miRNAs in tumor microenvironment. J. Exp. Clin. Cancer Res. 2020, 39, 67. [Google Scholar] [CrossRef]
- Santos, P.; Almeida, F. Role of Exosomal miRNAs and the Tumor Microenvironment in Drug Resistance. Cells 2020, 9, 1450. [Google Scholar] [CrossRef]
- Neviani, P.; Fabbri, M. Exosomic microRNAs in the Tumor Microenvironment. Front. Med. 2015, 2, 47. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kanda, T.; Yajima, M.; Ikuta, K. Epstein-Barr virus strain variation and cancer. Cancer Sci. 2019, 110, 1132–1139. [Google Scholar] [CrossRef] [PubMed]
- Nowalk, A.; Green, M. Epstein-Barr Virus. Microbiol. Spectr. 2016, 4, 127–134. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Odumade, O.A.; Hogquist, K.A.; Balfour, H.H., Jr. Progress and Problems in Understanding and Managing Primary Epstein-Barr Virus Infections. Clin. Microbiol. Rev. 2011, 24, 193–209. [Google Scholar] [CrossRef] [Green Version]
- Chetham, M.M.; Roberts, K.B. Infectious Mononucleosis in Adolescents. Pediatr. Ann. 1991, 20, 206–213. [Google Scholar] [CrossRef]
- Münz, C. Latency and lytic replication in Epstein–Barr virus-associated oncogenesis. Nat. Rev. Genet. 2019, 17, 691–700. [Google Scholar] [CrossRef] [Green Version]
- Wong, K.C.W.; Hui, E.P.; Lo, K.-W.; Lam, W.K.J.; Johnson, D.; Li, L.; Tao, Q.; Chan, K.C.A.; To, K.-F.; King, A.D.; et al. Nasopharyngeal carcinoma: An evolving paradigm. Nat. Rev. Clin. Oncol. 2021, 18, 679–695. [Google Scholar] [CrossRef]
- Saito, M.; Kono, K. Landscape of EBV-positive gastric cancer. Gastric Cancer 2021, 24, 983–989. [Google Scholar] [CrossRef]
- Shannon-Lowe, C.; Rickinson, A.B.; Bell, A.I. Epstein–Barr virus-associated lymphomas. Philos. Trans. R. Soc. B Biol. Sci. 2017, 372, 20160271. [Google Scholar] [CrossRef]
- Canitano, A.; Venturi, G.; Borghi, M.; Ammendolia, M.G.; Fais, S. Exosomes released in vitro from Epstein–Barr virus (EBV)-infected cells contain EBV-encoded latent phase mRNAs. Cancer Lett. 2013, 337, 193–199. [Google Scholar] [CrossRef]
- Gallo, A.; Vella, S.; Miele, M.; Timoneri, F.; Di Bella, M.; Bosi, S.; Sciveres, M.; Conaldi, P.G. Global profiling of viral and cellular non-coding RNAs in Epstein–Barr virus-induced lymphoblastoid cell lines and released exosome cargos. Cancer Lett. 2017, 388, 334–343. [Google Scholar] [CrossRef] [PubMed]
- Rashid, M.; Zadeh, L.R.; Baradaran, B.; Molavi, O.; Ghesmati, Z.; Sabzichi, M.; Ramezani, F. Up-down regulation of HIF-1α in cancer progression. Gene 2021, 798, 145796. [Google Scholar] [CrossRef] [PubMed]
- Davis, A.; Rapley, A.; Dawson, C.; Young, L.; Morris, M. The EBV-Encoded Oncoprotein, LMP1, Recruits and Transforms Fibroblasts via an ERK-MAPK-Dependent Mechanism. Pathogens 2021, 10, 982. [Google Scholar] [CrossRef] [PubMed]
- Aga, M.; Bentz, G.L.; Raffa, S.; Torrisi, M.R.; Kondo, S.; Wakisaka, N.; Yoshizaki, T.; Pagano, J.S.; Shackelford, J. Exosomal HIF1α supports invasive potential of nasopharyngeal carcinoma-associated LMP1-positive exosomes. Oncogene 2014, 33, 4613–4622. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Meckes, D.G., Jr.; Shair, K.H.Y.; Marquitz, A.R.; Kung, C.-P.; Edwards, R.H.; Raab-Traub, N. Human tumor virus utilizes exosomes for intercellular communication. Proc. Natl. Acad. Sci. USA 2010, 107, 20370–20375. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Flanagan, J.; Middeldorp, J.; Sculley, T. Localization of the Epstein–Barr virus protein LMP 1 to exosomes. J. Gen. Virol. 2003, 84, 1871–1879. [Google Scholar] [CrossRef] [PubMed]
- Klibi, J.; Niki, T.; Adhikary, D.; Mautner, J.; Busson, P.; Riedel, A.; Pioche-Durieu, C.; Souquere, S.; Rubinstein, E.; Le Moulec, S.; et al. Blood diffusion and Th1-suppressive effects of galectin-9–containing exosomes released by Epstein-Barr virus–infected nasopharyngeal carcinoma cells. Blood 2009, 113, 1957–1966. [Google Scholar] [CrossRef] [Green Version]
- Skalsky, R.L.; Cullen, B.R. EBV Noncoding RNAs. Curr. Top. Microbiol. Immunol. 2015, 391, 181–217. [Google Scholar] [CrossRef] [Green Version]
- Thorsen, S.B.; Obad, S.; Jensen, N.F.; Stenvang, J.; Kauppinen, S. The Therapeutic Potential of MicroRNAs in Cancer. Cancer J. 2012, 18, 275–284. [Google Scholar] [CrossRef]
- Zhang, S.; Yang, J.; Shen, L. Extracellular vesicle-mediated regulation of tumor angiogenesis— implications for anti-angiogenesis therapy. J. Cell. Mol. Med. 2021, 25, 2776–2785. [Google Scholar] [CrossRef]
- Wang, J.; Jiang, Q.; Faleti, O.D.; Tsang, C.-M.; Zhao, M.; Wu, G.; Tsao, S.-W.; Fu, M.; Chen, Y.; Ding, T.; et al. Exosomal Delivery of AntagomiRs Targeting Viral and Cellular MicroRNAs Synergistically Inhibits Cancer Angiogenesis. Mol. Ther. Nucleic Acids 2020, 22, 153–165. [Google Scholar] [CrossRef] [PubMed]
- Ahmed, W.; Philip, P.S.; Tariq, S.; Khan, G. Epstein-Barr Virus-Encoded Small RNAs (EBERs) Are Present in Fractions Related to Exosomes Released by EBV-Transformed Cells. PLoS ONE 2014, 9, e99163. [Google Scholar] [CrossRef] [PubMed]
- Ahmed, W.; Tariq, S.; Khan, G. Tracking EBV-encoded RNAs (EBERs) from the nucleus to the excreted exosomes of B-lymphocytes. Sci. Rep. 2018, 8, 15438. [Google Scholar] [CrossRef] [PubMed]
- Baglio, S.R.; van Eijndhoven, M.A.J.; Koppers-Lalic, D.; Berenguer, J.; Lougheed, S.M.; Gibbs, S.; Léveillé, N.; Rinkel, R.N.P.M.; Hopmans, E.S.; Swaminathan, S.; et al. Sensing of latent EBV infection through exosomal transfer of 5′pppRNA. Proc. Natl. Acad. Sci. USA 2016, 113, E587–E596. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Komano, J.; Maruo, S.; Kurozumi, K.; Oda, T.; Takada, K. Oncogenic Role of Epstein-Barr Virus-Encoded RNAs in Burkitt’s Lymphoma Cell Line Akata. J. Virol. 1999, 73, 9827–9831. [Google Scholar] [CrossRef] [Green Version]
- Yamamoto, N.; Takizawa, T.; Iwanaga, Y.; Shimizu, N.; Yamamoto, N. Malignant transformation of B lymphoma cell line BJAB by Epstein-Barr virus-encoded small RNAs. FEBS Lett. 2000, 484, 153–158. [Google Scholar] [CrossRef] [Green Version]
- Zhang, G.; Zong, J.; Lin, S.; Verhoeven, R.J.; Tong, S.; Chen, Y.; Ji, M.; Cheng, W.; Tsao, S.; Lung, M.; et al. CirculatingEpstein–Barr virus microRNAs miR-BART7and miR-BART13as biomarkers for nasopharyngeal carcinoma diagnosis and treatment. Int. J. Cancer 2014, 136, E301–E312. [Google Scholar] [CrossRef]
- Yip, T.T.; Ngan, R.K.; Fong, A.H.; Law, S.C. Application of circulating plasma/serum EBV DNA in the clinical management of nasopharyngeal carcinoma. Oral Oncol. 2014, 50, 527–538. [Google Scholar] [CrossRef]
- de Villiers, E.-M.; Fauquet, C.; Broker, T.R.; Bernard, H.-U.; zur Hausen, H. Classification of papillomaviruses. Virology 2004, 324, 17–27. [Google Scholar] [CrossRef] [Green Version]
- Petca, A.; Borislavschi, A.; Zvanca, M.E.; Petca, R.-C.; Sandru, F.; Dumitrascu, M.C. Non-sexual HPV transmission and role of vaccination for a better future (Review). Exp. Ther. Med. 2020, 20, 186. [Google Scholar] [CrossRef]
- Hirth, J. Disparities in HPV vaccination rates and HPV prevalence in the United States: A review of the literature. Hum. Vaccines Immunother. 2018, 15, 146–155. [Google Scholar] [CrossRef] [PubMed]
- Boda, D.; Docea, A.O.; Calina, D.; Ilie, M.A.; Caruntu, C.; Zurac, S.; Neagu, M.; Constantin, C.; Branisteanu, D.E.; Voiculescu, V.; et al. Human papilloma virus: Apprehending the link with carcinogenesis and unveiling new research avenues (Review). Int. J. Oncol. 2018, 52, 637–655. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Basukala, O.; Banks, L. The Not-So-Good, the Bad and the Ugly: HPV E5, E6 and E7 Oncoproteins in the Orchestration of Carcinogenesis. Viruses 2021, 13, 1892. [Google Scholar] [CrossRef] [PubMed]
- Pal, A.; Kundu, R. Human Papillomavirus E6 and E7: The Cervical Cancer Hallmarks and Targets for Therapy. Front. Microbiol. 2020, 10, 3116. [Google Scholar] [CrossRef] [Green Version]
- Iuliano, M.; Mangino, G.; Chiantore, M.V.; Zangrillo, M.S.; Accardi, R.; Tommasino, M.; Fiorucci, G.; Romeo, G. Human Papillomavirus E6 and E7 oncoproteins affect the cell microenvironment by classical secretion and extracellular vesicles delivery of inflammatory mediators. Cytokine 2018, 106, 182–189. [Google Scholar] [CrossRef]
- Di Bonito, P.; Ridolfi, B.; Columba-Cabezas, S.; Giovannelli, A.; Chiozzini, C.; Manfredi, F.; Anticoli, S.; Arenaccio, C.; Federico, M. HPV-E7 Delivered by Engineered Exosomes Elicits a Protective CD8+ T Cell-Mediated Immune Response. Viruses 2015, 7, 1079–1099. [Google Scholar] [CrossRef] [Green Version]
- Ludwig, S.; Sharma, P.; Theodoraki, M.-N.; Pietrowska, M.; Yerneni, S.S.; Lang, S.; Ferrone, S.; Whiteside, T.L. Molecular and Functional Profiles of Exosomes From HPV(+) and HPV(−) Head and Neck Cancer Cell Lines. Front. Oncol. 2018, 8, 445. [Google Scholar] [CrossRef]
- Honegger, A.; Leitz, J.; Bulkescher, J.; Hoppe-Seyler, K.; Hoppe-Seyler, F. Silencing of human papillomavirus (HPV)E6/E7oncogene expression affects both the contents and the amounts of extracellular microvesicles released from HPV-positive cancer cells. Int. J. Cancer 2013, 133, 1631–1642. [Google Scholar] [CrossRef]
- Honegger, A.; Schilling, D.; Bastian, S.; Sponagel, J.; Kuryshev, V.; Sültmann, H.; Scheffner, M.; Hoppe-Seyler, K.; Hoppe-Seyler, F. Dependence of Intracellular and Exosomal microRNAs on Viral E6/E7 Oncogene Expression in HPV-positive Tumor Cells. PLoS Pathog. 2015, 11, e1004712. [Google Scholar] [CrossRef]
- Chiantore, M.V.; Mangino, G.; Iuliano, M.; Zangrillo, M.S.; De Lillis, I.; Vaccari, G.; Accardi, R.; Tommasino, M.; Cabezas, S.C.; Federico, M.; et al. Human papillomavirus E6 and E7 oncoproteins affect the expression of cancer-related microRNAs: Additional evidence in HPV-induced tumorigenesis. J. Cancer Res. Clin. Oncol. 2016, 142, 1751–1763. [Google Scholar] [CrossRef]
- Harden, M.E.; Munger, K. Human papillomavirus 16 E6 and E7 oncoprotein expression alters microRNA expression in extracellular vesicles. Virology 2017, 508, 63–69. [Google Scholar] [CrossRef] [PubMed]
- Mata-Rocha, M.; Rodríguez-Hernández, R.M.; Chávez-Olmos, P.; Garrido, E.; Robles-Vázquez, C.; Aguilar-Ruiz, S.; Torres-Aguilar, H.; González-Torres, C.; Gaytan-Cervantes, J.; Mejía-Aranguré, J.M.; et al. Presence of HPV DNA in extracellular vesicles from HeLa cells and cervical samples. Enferm. Infecc. Y Microbiol. Clínica 2020, 38, 159–165. [Google Scholar] [CrossRef]
- Cocuzza, C.E.; Martinelli, M.; Sina, F.; Piana, A.; Sotgiu, G.; Dell’Anna, T.; Musumeci, R. Human papillomavirus DNA detection in plasma and cervical samples of women with a recent history of low grade or precancerous cervical dysplasia. PLoS ONE 2017, 12, e0188592. [Google Scholar] [CrossRef] [PubMed]
- De Carolis, S.; Storci, G.; Ceccarelli, C.; Savini, C.; Gallucci, L.; Sansone, P.; Santini, D.; Seracchioli, R.; Taffurelli, M.; Fabbri, F.; et al. HPV DNA Associates With Breast Cancer Malignancy and It Is Transferred to Breast Cancer Stromal Cells by Extracellular Vesicles. Front. Oncol. 2019, 9, 860. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ambrosio, M.R.; Vernillo, R.; De Carolis, S.; Carducci, A.; Mundo, L.; Ginori, A.; Rocca, B.J.; Nardone, V.; Fei, A.L.; Carfagno, T.; et al. Putative Role of Circulating Human Papillomavirus DNA in the Development of Primary Squamous Cell Carcinoma of the Middle Rectum: A Case Report. Front. Oncol. 2019, 9, 93. [Google Scholar] [CrossRef]
- Wang, Z.; Li, F.; Rufo, J.; Chen, C.; Yang, S.; Li, L.; Zhang, J.; Cheng, J.; Kim, Y.; Wu, M.; et al. Acoustofluidic Salivary Exosome Isolation. J. Mol. Diagn. 2019, 22, 50–59. [Google Scholar] [CrossRef] [Green Version]
- Di Cola, G.; Fantilli, A.C.; Pisano, M.B.; Ré, V.E. Foodborne transmission of hepatitis A and hepatitis E viruses: A literature review. Int. J. Food Microbiol. 2020, 338, 108986. [Google Scholar] [CrossRef]
- Pirozzolo, J.J.; LeMay, D.C. Blood-Borne Infections. Clin. Sports Med. 2007, 26, 425–431. [Google Scholar] [CrossRef]
- Cavalheiro, N.D.P. Sexual transmission of hepatitis C. Rev. Do Inst. De Med. Trop. De São Paulo 2007, 49, 271–277. [Google Scholar] [CrossRef] [Green Version]
- Farci, P.; Niro, G.; Zamboni, F.; Diaz, G. Hepatitis D Virus and Hepatocellular Carcinoma. Viruses 2021, 13, 830. [Google Scholar] [CrossRef]
- Lanini, S.; Ustianowski, A.; Pisapia, R.; Zumla, A.; Ippolito, G. Viral Hepatitis. Infect. Dis. Clin. N. Am. 2019, 33, 1045–1062. [Google Scholar] [CrossRef] [PubMed]
- Sagnelli, E.; Macera, M.; Russo, A.; Coppola, N.; Sagnelli, C. Epidemiological and etiological variations in hepatocellular carcinoma. Infection 2019, 48, 7–17. [Google Scholar] [CrossRef] [PubMed]
- Taylor, J.M. Infection by Hepatitis Delta Virus. Viruses 2020, 12, 648. [Google Scholar] [CrossRef] [PubMed]
- Abbas, Z. Hepatitis D and hepatocellular carcinoma. World J. Hepatol. 2015, 7, 777–786. [Google Scholar] [CrossRef]
- Kouwaki, T.; Fukushima, Y.; Daito, T.; Sanada, T.; Yamamoto, N.; Mifsud, E.J.; Leong, C.R.; Tsukiyama-Kohara, K.; Kohara, M.; Matsumoto, M.; et al. Extracellular Vesicles Including Exosomes Regulate Innate Immune Responses to Hepatitis B Virus Infection. Front. Immunol. 2016, 7, 335. [Google Scholar] [CrossRef] [Green Version]
- Kakizaki, M.; Yamamoto, Y.; Yabuta, S.; Kurosaki, N.; Kagawa, T.; Kotani, A. The immunological function of extracellular vesicles in hepatitis B virus-infected hepatocytes. PLoS ONE 2018, 13, e0205886. [Google Scholar] [CrossRef]
- Liu, D.; Li, P.; Guo, J.; Li, L.; Guo, B.; Jiao, H.; Wu, J.; Chen, J. Exosomes derived from HBV-associated liver cancer promote chemoresistance by upregulating chaperone-mediated autophagy. Oncol. Lett. 2018, 17, 323–331. [Google Scholar] [CrossRef] [Green Version]
- Yang, X.; Li, H.; Sun, H.; Fan, H.; Hu, Y.; Liu, M.; Li, X.; Tang, H. Hepatitis B Virus-Encoded MicroRNA Controls Viral Replication. J. Virol. 2017, 91, e01919-16. [Google Scholar] [CrossRef] [Green Version]
- Zhao, X.; Sun, L.; Mu, T.; Yi, J.; Ma, C.; Xie, H.; Liu, M.; Tang, H. An HBV-encoded miRNA activates innate immunity to restrict HBV replication. J. Mol. Cell Biol. 2019, 12, 263–276. [Google Scholar] [CrossRef]
- Tang, J.; Xiao, X.; Jiang, Y.; Tian, Y.; Peng, Z.; Yang, M.; Xu, Z.; Gong, G. miR-3 Encoded by Hepatitis B Virus Downregulates PTEN Protein Expression and Promotes Cell Proliferation. J. Hepatocell. Carcinoma 2020, 7, 257–269. [Google Scholar] [CrossRef]
- Chavalit, T.; Nimsamer, P.; Sirivassanametha, K.; Anuntakarun, S.; Saengchoowong, S.; Tangkijvanich, P.; Payungporn, S. Hepatitis B Virus-Encoded MicroRNA (HBV-miR-3) Regulates Host Gene PPM1A Related to Hepatocellular Carcinoma. MicroRNA 2020, 9, 232–239. [Google Scholar] [CrossRef] [PubMed]
- Gan, W.; Chen, X.; Wu, Z.; Zhu, X.; Liu, J.; Wang, T.; Gao, Z. The relationship between serum exosome HBV-miR-3 and current virological markers and its dynamics in chronic hepatitis B patients on antiviral treatment. Ann. Transl. Med. 2022, 10, 536. [Google Scholar] [CrossRef] [PubMed]
- Liu, W.; Hu, J.; Zhou, K.; Chen, F.; Wang, Z.; Liao, B.; Dai, Z.; Cao, Y.; Fan, J.; Zhou, J. Serum exosomal miR-125b is a novel prognostic marker for hepatocellular carcinoma. OncoTargets Ther. 2017, 10, 3843–3851. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kapoor, N.R.; Chadha, R.; Kumar, S.; Choedon, T.; Reddy, V.S.; Kumar, V. The HBx gene of hepatitis B virus can influence hepatic microenvironment via exosomes by transferring its mRNA and protein. Virus Res. 2017, 240, 166–174. [Google Scholar] [CrossRef] [PubMed]
- Ali, A.; Abdel-Hafiz, H.; Suhail, M.; Al-Mars, A.; Zakaria, M.K.; Fatima, K.; Ahmad, S.; Azhar, E.; Chaudhary, A.; Qadri, I. Hepatitis B virus, HBx mutants and their role in hepatocellular carcinoma. World J. Gastroenterol. 2014, 20, 10238–10248. [Google Scholar] [CrossRef] [PubMed]
- Ramakrishnaiah, V.; Thumann, C.; Fofana, I.; Habersetzer, F.; Pan, Q.; de Ruiter, P.E.; Willemsen, R.; Demmers, J.A.A.; Raj, V.S.; Jenster, G.; et al. Exosome-mediated transmission of hepatitis C virus between human hepatoma Huh7.5 cells. Proc. Natl. Acad. Sci. USA 2013, 110, 13109–13113. [Google Scholar] [CrossRef] [Green Version]
- Saha, B.; Kodys, K.; Adejumo, A.; Szabo, G. Circulating and Exosome-Packaged Hepatitis C Single-Stranded RNA Induce Monocyte Differentiation via TLR7/8 to Polarized Macrophages and Fibrocytes. J. Immunol. 2017, 198, 1974–1984. [Google Scholar] [CrossRef] [Green Version]
- Malik, M.A.; Mirza, J.I.A.; Umar, M.; Manzoor, S. CD81+ Exosomes Play a Pivotal Role in the Establishment of Hepatitis C Persistent Infection and Contribute Toward the Progression of Hepatocellular Carcinoma. Viral Immunol. 2019, 32, 453–462. [Google Scholar] [CrossRef]
- Duvic, M. HIV and Skin Disease: The Molecular Biology of the Human Immunodeficiency Virus. Am. J. Med. Sci. 1992, 304, 180–187. [Google Scholar] [CrossRef]
- Neto, M.M.D.S.; Brites, C.; Borges, H. Cancer during HIV infection. APMIS 2020, 128, 121–128. [Google Scholar] [CrossRef]
- Ruffieux, Y.; Muchengeti, M.; Egger, M.; Efthimiou, O.; Bartels, L.; Olago, V.; Davidović, M.; Dhokotera, T.; Bohlius, J.; Singh, E.; et al. Immunodeficiency and Cancer in 3.5 Million People Living With Human Immunodeficiency Virus (HIV): The South African HIV Cancer Match Study. Clin. Infect. Dis. 2021, 73, e735–e744. [Google Scholar] [CrossRef] [PubMed]
- Bannwarth, S.; Gatignol, A. HIV-1 TAR RNA: The Target of Molecular Interactions Between the Virus and its Host. Curr. HIV Res. 2005, 3, 61–71. [Google Scholar] [CrossRef] [PubMed]
- Narayanan, A.; Iordanskiy, S.; Das, R.; Van Duyne, R.; Santos, S.; Jaworski, E.; Guendel, I.; Sampey, G.; Dalby, E.; Iglesias-Ussel, M.; et al. Exosomes Derived from HIV-1-infected Cells Contain Trans-activation Response Element RNA. J. Biol. Chem. 2013, 288, 20014–20033. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sampey, G.C.; Saifuddin, M.; Schwab, A.; Barclay, R.; Punya, S.; Chung, M.-C.; Hakami, R.M.; Zadeh, M.A.; Lepene, B.; Klase, Z.A.; et al. Exosomes from HIV-1-infected Cells Stimulate Production of Pro-inflammatory Cytokines through Trans-activating Response (TAR) RNA. J. Biol. Chem. 2016, 291, 1251–1266. [Google Scholar] [CrossRef] [Green Version]
- Sharma, N.K. Exosomal packaging of trans-activation response element (TAR) RNA by HIV-1 infected cells: A pro-malignancy message delivery to cancer cells. Mol. Biol. Rep. 2019, 46, 3607–3612. [Google Scholar] [CrossRef]
- Chen, L.; Feng, Z.; Yue, H.; Bazdar, D.; Mbonye, U.; Zender, C.; Harding, C.V.; Bruggeman, L.; Karn, J.; Sieg, S.F.; et al. Exosomes derived from HIV-1-infected cells promote growth and progression of cancer via HIV TAR RNA. Nat. Commun. 2018, 9, 4585. [Google Scholar] [CrossRef] [Green Version]
- Chen, L.; Feng, Z.; Yuan, G.; Emerson, C.C.; Stewart, P.L.; Ye, F.; Jin, G. Human Immunodeficiency Virus-Associated Exosomes Promote Kaposi’s Sarcoma-Associated Herpesvirus Infection via the Epidermal Growth Factor Receptor. J. Virol. 2020, 94, e01782-19. [Google Scholar] [CrossRef] [Green Version]
- Stelzle, D.; Tanaka, L.F.; Lee, K.K.; Ibrahim Khalil, A.; Baussano, I.; Shah, A.S.V.; McAllister, D.A.; Gottlieb, S.L.; Klug, S.J.; Winkler, A.S.; et al. Estimates of the global burden of cervical cancer associated with HIV. Lancet Glob. Health 2021, 9, e161–e169. [Google Scholar] [CrossRef]
- Zayats, R.; Murooka, T.T.; McKinnon, L.R. HPV and the Risk of HIV Acquisition in Women. Front. Cell. Infect. Microbiol. 2022, 12, 814948. [Google Scholar] [CrossRef]
- Chibwesha, C.J.; Stringer, J.S.A. Cervical Cancer as a Global Concern: Contributions of the Dual Epidemics of HPV and HIV. JAMA 2019, 322, 1558–1560. [Google Scholar] [CrossRef]
- Du, P. Human Papillomavirus Infection and Cervical Cancer in HIV+ Women. Cancer Res. Treat. 2018, 177, 105–129. [Google Scholar] [CrossRef]
- Hu, Z.; Ma, D. The precision prevention and therapy of HPV-related cervical cancer: New concepts and clinical implications. Cancer Med. 2018, 7, 5217–5236. [Google Scholar] [CrossRef] [PubMed]
- Li, H.; Chi, X.; Li, R.; Ouyang, J.; Chen, Y. HIV-1-infected cell-derived exosomes promote the growth and progression of cervical cancer. Int. J. Biol. Sci. 2019, 15, 2438–2447. [Google Scholar] [CrossRef] [PubMed] [Green Version]
Cancers | Components in Exosomes | Function | References | |
---|---|---|---|---|
EBV-related Cancers | HIF-1α | Promote the migration and invasion of NPC cells | [64] | |
LMP1 | Promotes migration and invasion of EBV-associated tumor cells Involved in immune regulation | [65,66] | ||
galectin-9 | Involved in immune regulation, inducing apoptosis of Th1 lymphocytes | [67] | ||
miR-BART-10-5p | Promote angiogenesis in nasopharyngeal carcinoma | [71] | ||
miR-18a | ||||
EBERs | Trigger antiviral immunity | [74] | ||
Induction of malignant transformation of EBV-negative cell lines | [75,76] | |||
HPV-related cancers | HPV E6/E7 | Induces CD8+ T cell immunity and inhibits tumor growth | [86] | |
Anti-tumor immune function in head and neck cancer | [87] | |||
HPV DNA | Activates breast cancer stromal cells and promotes breast cancer cell proliferation and invasion | [94] | ||
Polarize macrophages into M2 type and play a carcinogenic role | [95] | |||
Hepatitis Virus-associated Cancers | HBV | HBV-associated exosomes | Affect HBV immunity | [105,106] |
Induction of chemoresistance in hepatocellular carcinoma | [107] | |||
HBV-miR-3 | Inhibition of HBV replication in hepatocellular carcinoma and promotion of M1 macrophage polarization | [109] | ||
Enhanced hepatocellular carcinoma proliferation and invasion | [110,111] | |||
HCV | HCV-RNA | Facilitates immune escape of HCV in liver cancer cells | [116] | |
Induction of monocyte differentiation and M2 macrophage polarization | [117] | |||
HIV-related Cancers | TAR RNA | Promote tumor cell proliferation | [126] | |
Promotes KSHV infection of oral epithelial cells | [127] | |||
miR-155-5p | Promote tumor cell proliferation, stemness and tumorigenicity | [133] |
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Li, J.; Zhang, Y.; Luo, B. Effects of Exosomal Viral Components on the Tumor Microenvironment. Cancers 2022, 14, 3552. https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14143552
Li J, Zhang Y, Luo B. Effects of Exosomal Viral Components on the Tumor Microenvironment. Cancers. 2022; 14(14):3552. https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14143552
Chicago/Turabian StyleLi, Jing, Yan Zhang, and Bing Luo. 2022. "Effects of Exosomal Viral Components on the Tumor Microenvironment" Cancers 14, no. 14: 3552. https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14143552