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Interferon-α-secreting mesenchymal stem cells exert potent antitumor effect in vivo

Oncogene volume 33, pages 5047–5052 (2014)Cite this article

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Abstract

Mesenchymal stem cells (MSCs) are a kind of adult stem cells that can be isolated easily from bone marrow, adipose tissue, umbilical cord and many other tissues. MSCs have been shown to specifically migrate to inflammatory sites, including tumors, and hold great promise as tumor-specific vectors to deliver antitumor agents. Interferon-α (IFNα) has been used in clinic to treat various types of tumors; however, because of its short half-life, significant therapeutic effects require high doses that often results in serious side effects. Here, we tested whether MSCs continuingly secreting IFNα can exert a persistent antitumor effect and eliminate the side effects associated with high clinical doses of recombinant IFNα. We found that even a small number of IFNα-secreting MSCs could potently halt B16 tumor growth in vivo. The antitumor activity of IFNα-secreting MSCs was largely abolished in immunodeficient mice, an effect largely attributed to natural killer cells and CD8+ T cells. Therefore, IFNα-secreting MSCs provide an innovative strategy for tumor therapy.

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References

  1. Bianco P, Robey PG, Simmons PJ . Mesenchymal stem cells: revisiting history, concepts, and assays. Cell Stem Cell 2008; 2: 313–319.

    Article  CAS  Google Scholar 

  2. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999; 284: 143–147.

    Article  CAS  Google Scholar 

  3. Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ et al. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng 2001; 7: 211–228.

    Article  CAS  Google Scholar 

  4. Uccelli A, Moretta L, Pistoia V . Mesenchymal stem cells in health and disease. Nat Rev Immunol 2008; 8: 726–736.

    Article  CAS  Google Scholar 

  5. Ren G, Zhao X, Wang Y, Zhang X, Chen X, Xu C et al. CCR2-dependent recruitment of macrophages by tumor-educated mesenchymal stromal cells promotes tumor development and is mimicked by TNFalpha. Cell Stem Cell 2012; 11: 812–824.

    Article  CAS  Google Scholar 

  6. Horwitz EM, Le Blanc K, Dominici M, Mueller I, Slaper-Cortenbach I, Marini FC et al. Clarification of the nomenclature for MSC: The International Society for Cellular Therapy position statement. Cytotherapy 2005; 7: 393–395.

    Article  CAS  Google Scholar 

  7. Kolf CM, Cho E, Tuan RS . Mesenchymal stromal cells. Biology of adult mesenchymal stem cells: regulation of niche, self-renewal and differentiation. Arthritis Res Ther 2007; 9: 204.

    Article  Google Scholar 

  8. Horwitz EM, Prockop DJ, Fitzpatrick LA, Koo WW, Gordon PL, Neel M et al. Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta. Nat Med 1999; 5: 309–313.

    Article  CAS  Google Scholar 

  9. Shi Y, Hu G, Su J, Li W, Chen Q, Shou P et al. Mesenchymal stem cells: a new strategy for immunosuppression and tissue repair. Cell Res 2010; 20: 510–518.

    Article  CAS  Google Scholar 

  10. Ren G, Chen X, Dong F, Li W, Ren X, Zhang Y et al. Concise review: mesenchymal stem cells and translational medicine: emerging issues. Stem Cells Transl Med 2012; 1: 51–58.

    Article  CAS  Google Scholar 

  11. Ranganath SH, Levy O, Inamdar MS, Karp JM . Harnessing the mesenchymal stem cell secretome for the treatment of cardiovascular disease. Cell Stem Cell 2012; 10: 244–258.

    Article  CAS  Google Scholar 

  12. Sensebe L, Tarte K, Galipeau J, Krampera M, Martin I, Phinney DG et al. Limited acquisition of chromosomal aberrations in human adult mesenchymal stromal cells. Cell Stem Cell 2012; 10: 9–10, author reply 10-11.

    Article  CAS  Google Scholar 

  13. Karp JM, Leng Teo GS . Mesenchymal stem cell homing: the devil is in the details. Cell Stem Cell 2009; 4: 206–216.

    Article  CAS  Google Scholar 

  14. Kidd S, Spaeth E, Dembinski JL, Dietrich M, Watson K, Klopp A et al. Direct evidence of mesenchymal stem cell tropism for tumor and wounding microenvironments using in vivo bioluminescent imaging. Stem Cells 2009; 27: 2614–2623.

    Article  CAS  Google Scholar 

  15. Wang H, Cao F, De A, Cao Y, Contag C, Gambhir SS et al. Trafficking mesenchymal stem cell engraftment and differentiation in tumor-bearing mice by bioluminescence imaging. Stem Cells 2009; 27: 1548–1558.

    Article  CAS  Google Scholar 

  16. Loebinger MR, Kyrtatos PG, Turmaine M, Price AN, Pankhurst Q, Lythgoe MF et al. Magnetic resonance imaging of mesenchymal stem cells homing to pulmonary metastases using biocompatible magnetic nanoparticles. Cancer Res 2009; 69: 8862–8867.

    Article  CAS  Google Scholar 

  17. Studeny M, Marini FC, Champlin RE, Zompetta C, Fidler IJ, Andreeff M . Bone marrow-derived mesenchymal stem cells as vehicles for interferon-beta delivery into tumors. Cancer Res 2002; 62: 3603–3608.

    CAS  Google Scholar 

  18. Kim SM, Lim JY, Park SI, Jeong CH, Oh JH, Jeong M et al. Gene therapy using TRAIL-secreting human umbilical cord blood-derived mesenchymal stem cells against intracranial glioma. Cancer Res 2008; 68: 9614–9623.

    Article  CAS  Google Scholar 

  19. Bracarda S, Eggermont AM, Samuelsson J . Redefining the role of interferon in the treatment of malignant diseases. Eur J Cancer 2009; 46: 284–297.

    Article  Google Scholar 

  20. Pestka S . The interferons: 50 years after their discovery, there is much more to learn. J Biol Chem 2007; 282: 20047–20051.

    Article  CAS  Google Scholar 

  21. Pestka S . A dance between interferon-alpha/beta and p53 demonstrates collaborations in tumor suppression and antiviral activities. Cancer Cell 2003; 4: 85–87.

    Article  CAS  Google Scholar 

  22. Cerwenka A, Lanier LL . Natural killer cells, viruses and cancer. Nat Rev Immunol 2001; 1: 41–49.

    Article  CAS  Google Scholar 

  23. Hainaut P, Plymoth A . Targeting the hallmarks of cancer: towards a rational approach to next-generation cancer therapy. Curr Opin Oncol 2012; 25: 50–51.

    Article  Google Scholar 

  24. Wang B, Rosano JM, Cheheltani R, Achary MP, Kiani MF . Towards a targeted multi-drug delivery approach to improve therapeutic efficacy in breast cancer. Expert Opin Drug Deliv 2010; 7: 1159–1173.

    Article  CAS  Google Scholar 

  25. Keating A . Mesenchymal stromal cells: new directions. Cell Stem Cell 2012; 10: 709–716.

    Article  CAS  Google Scholar 

  26. Zou WB, Zheng HL, He TC, Chang JJ, Fu YX, Fan WM . LIGHT delivery to tumors by mesenchymal stem cells mobilizes an effective antitumor immune response. Cancer Rese 2012; 72: 2980–2989.

    Article  CAS  Google Scholar 

  27. Elzaouk L, Moelling K, Pavlovic J . Anti-tumor activity of mesenchymal stem cells producing IL-12 in a mouse melanoma model. Exp Dermatol 2006; 15: 865–874.

    Article  CAS  Google Scholar 

  28. Vanneman M, Dranoff G . Combining immunotherapy and targeted therapies in cancer treatment. Nat Rev Cancer 2012; 12: 237–251.

    Article  CAS  Google Scholar 

  29. Vivier E, Ugolini S, Blaise D, Chabannon C, Brossay L . Targeting natural killer cells and natural killer T cells in cancer. Nat Rev Immunol 2012; 12: 239–252.

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported by grants from Scientific Innovation Project of the Chinese Academy of Science (XDA 01040107 and XDA 01040110), the Ministry of Science and Technology of China (2010CB945600 and 2011DFA30630), the National Science and Technology Project of China (31010103908 and 81273316), Shanghai Municipal Key Projects of Basic Research (12JC1409200), Shanghai Municipal Natural Science Foundation (12ZR1452600), the Knowledge Innovation Program of Shanghai Institutes for Biological Sciences and the Chinese Academy of Sciences (2012KIP202).

Author contributions

YS and YW conceived this project, designed experiments and analyzed data and prepared the manuscript; CX conceived this project, designed and performed experiments, analyzed data and prepared the manuscript; LL, QC, GC, YW, YH and YH performed experiments.

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Authors and Affiliations

  1. Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine, Shanghai, China

    C Xu, L Lin, G Cao, Q Chen, P Shou, Y Huang, Y Han, Y Wang & Y Shi

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  1. C Xu
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  2. L Lin
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  3. G Cao
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  4. Q Chen
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  7. Y Han
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  8. Y Wang
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  9. Y Shi
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Correspondence to Y Wang or Y Shi.

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Xu, C., Lin, L., Cao, G. et al. Interferon-α-secreting mesenchymal stem cells exert potent antitumor effect in vivo. Oncogene 33, 5047–5052 (2014). https://doi.org/10.1038/onc.2013.458

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