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Mesenchymal Stem Cells in Cancer

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Abstract

It is becoming increasingly evident that stromal cells such as macrophages, mast cells, adipocytes and mesenchymal cells associated with tumors significantly contribute to tumorigenesis. Some types of cancer indeed profoundly rely on extrinsic signals afforded by infiltrating or neighbouring cells for survival, proliferation and dissemination. Tissue disruption that results from tumor growth further activates tissue repair and inflammatory reactions that significantly shape the nature of the developing tumors. Over the past recent years, several studies have revealed that mesenchymal stem cells (MSCs) are recruited to tumors and play a particularly important role in the regulation of both solid and haematological malignancies. The tumor-homing properties of MSCs have further led to studies investigating their therapeutic use as targeted delivery vehicles of gene products. I hereafter discuss the role of MSCs in cancer.

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References

  1. Stagg, J. (2007). Immune regulation by mesenchymal stem cells: Two sides to the coin. Tissue Antigens, 69(1), 1–9.

    Article  PubMed  CAS  Google Scholar 

  2. Gang, E. J., Bosnakovski, D., Figueiredo, C. A., Visser, J. W., & Perlingeiro, R. C. (2007). SSEA-4 identifies mesenchymal stem cells from bone marrow. Blood, 109(4), 1743–1751.

    Article  PubMed  CAS  Google Scholar 

  3. Stagg, J., Pommey, S., Eliopoulos, N., & Galipeau, J. (2006). Interferon-gamma-stimulated marrow stromal cells: A new type of nonhematopoietic antigen-presenting cell. Blood, 107(6), 2570–2577.

    Article  PubMed  CAS  Google Scholar 

  4. Krampera, M., Cosmi, L., Angeli, R., Pasini, A., Liotta, F., Andreini, A., et al. (2006). Role for interferon-gamma in the immunomodulatory activity of human bone marrow mesenchymal stem cells. Stem Cells, 24(2), 386–398.

    Article  PubMed  CAS  Google Scholar 

  5. Massague, J., Blain, S. W., & Lo, R. S. (2000). TGFbeta signaling in growth control, cancer, and heritable disorders. Cell, 103(2), 295–309.

    Article  PubMed  CAS  Google Scholar 

  6. Mishra, L., Derynck, R., & Mishra, B. (2005). Transforming growth factor-beta signaling in stem cells and cancer. Science, 310(5745), 68–71.

    Article  PubMed  CAS  Google Scholar 

  7. Gregory, C. A., Perry, A. S., Reyes, E., Conley, A., Gunn, W. G., & Prockop, D. J. (2005). Dkk-1-derived synthetic peptides and lithium chloride for the control and recovery of adult stem cells from bone marrow. Journal of Biological Chemistry, 280(3), 2309–2323.

    Article  PubMed  CAS  Google Scholar 

  8. Spees, J. L., Olson, S. D., Ylostalo, J., Lynch, P. J., Smith, J., Perry, A., et al. (2003). Differentiation, cell fusion, and nuclear fusion during ex vivo repair of epithelium by human adult stem cells from bone marrow stroma. Proceedings of the National Academy of Sciences of the United States of America, 100(5), 2397–2402.

    Article  PubMed  CAS  Google Scholar 

  9. Gnecchi, M., He, H., Liang, O. D., Melo, L. G., Morello, F., Mu, H., et al. (2005). Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells. Nature Medicine, 11(4), 367–368.

    Article  PubMed  CAS  Google Scholar 

  10. Li, Y., Chen, J., Chen, X. G., Wang, L., Gautam, S. C., Xu, Y. X., et al. (2002). Human marrow stromal cell therapy for stroke in rat: Neurotrophins and functional recovery. Neurology, 59(4), 514–523.

    PubMed  CAS  Google Scholar 

  11. Dwyer, R. M., Potter-Beirne, S. M., Harrington, K. A., Lowery, A. J., Hennessy, E., Murphy, J. M., et al. (2007). Monocyte chemotactic protein-1 secreted by primary breast tumors stimulates migration of mesenchymal stem cells. Clinical Cancer Research, 13(17), 5020–5027.

    Article  PubMed  CAS  Google Scholar 

  12. Honczarenko, M., Le, Y., Swierkowski, M., Ghiran, I., Glodek, A. M., & Silberstein, L. E. (2006). Human bone marrow stromal cells express a distinct set of biologically functional chemokine receptors. Stem Cells, 24(4), 1030–1041.

    Article  PubMed  CAS  Google Scholar 

  13. Nakamura, K., Ito, Y., Kawano, Y., Kurozumi, K., Kobune, M., Tsuda, H., et al. (2004). Antitumor effect of genetically engineered mesenchymal stem cells in a rat glioma model. Gene Therapy, 11(14), 1155–1164.

    Article  PubMed  CAS  Google Scholar 

  14. Nakamizo, A., Marini, F., Amano, T., Khan, A., Studeny, M., Gumin, J., et al. (2005). Human bone marrow-derived mesenchymal stem cells in the treatment of gliomas. Cancer Research, 65(8), 3307–3318 Apr 15.

    PubMed  CAS  Google Scholar 

  15. Studeny, M., Marini, F. C., Dembinski, J. L., Zompetta, C., Cabreira-Hansen, M., Bekele, B. N., et al. (2004). Mesenchymal stem cells: Potential precursors for tumor stroma and targeted-delivery vehicles for anticancer agents. Journal of the National Cancer Institute, 96(21), 1593–1603.

    Article  PubMed  CAS  Google Scholar 

  16. Hung, S. C., Deng, W. P., Yang, W. K., Liu, R. S., Lee, C. C., Su, T. C., et al. (2005). Mesenchymal stem cell targeting of microscopic tumors and tumor stroma development monitored by noninvasive in vivo positron emission tomography imaging. Clinical Cancer Research, 11(21), 7749–7756.

    Article  PubMed  CAS  Google Scholar 

  17. Komarova, S., Kawakami, Y., Stoff-Khalili, M. A., Curiel, D. T., & Pereboeva, L. (2006). Mesenchymal progenitor cells as cellular vehicles for delivery of oncolytic adenoviruses. Molecular Cancer Therapeutic, 5(3), 755–766.

    Article  CAS  Google Scholar 

  18. Khakoo, A. Y., Pati, S., Anderson, S. A., Reid, W., Elshal, M. F., Rovira, I. I., et al. (2006). Human mesenchymal stem cells exert potent antitumorigenic effects in a model of Kaposi’s sarcoma. Journal of Experimental Medicine, 203(5), 1235–1247.

    Article  PubMed  CAS  Google Scholar 

  19. Qiao, L., Xu, Z., Zhao, T., Zhao, Z., Shi, M., Zhao, R. C., et al. (2008). Suppression of tumorigenesis by human mesenchymal stem cells in a hepatoma model. Cell Research, 18(4), 500–507.

    Article  PubMed  CAS  Google Scholar 

  20. Karnoub, A. E., Dash, A. B., Vo, A. P., Sullivan, A., Brooks, M. W., Bell, G. W., et al. (2007). Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature, 449(7162), 557–563.

    Article  PubMed  CAS  Google Scholar 

  21. Haniffa, M. A., Wang, X. N., Holtick, U., Rae, M., Isaacs, J. D., Dickinson, A. M., et al. (2007). Adult human fibroblasts are potent immunoregulatory cells and functionally equivalent to mesenchymal stem cells. Journal of Immunology, 179(3), 1595–1604.

    CAS  Google Scholar 

  22. Ao, M., Franco, O. E., Park, D., Raman, D., Williams, K., & Hayward, S. W. (2007). Cross-talk between paracrine-acting cytokine and chemokine pathways promotes malignancy in benign human prostatic epithelium. Cancer Research, 67(9), 4244–4253.

    Article  PubMed  CAS  Google Scholar 

  23. Orimo, A., Gupta, P. B., Sgroi, D. C., Arenzana-Seisdedos, F., Delaunay, T., Naeem, R., et al. (2005). Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion. Cell, 121(3), 335–348.

    Article  PubMed  CAS  Google Scholar 

  24. Stagg, J., Lejeune, L., Paquin, A., & Galipeau, J. (2004). Marrow stromal cells for interleukin-2 delivery in cancer immunotherapy. Human Gene Therapy, 15(6), 597–608.

    Article  PubMed  CAS  Google Scholar 

  25. Gunn, W. G., Conley, A., Deininger, L., Olson, S. D., Prockop, D. J., & Gregory, C. A. (2006). A crosstalk between myeloma cells and marrow stromal cells stimulates production of DKK1 and interleukin-6: A potential role in the development of lytic bone disease and tumor progression in multiple myeloma. Stem Cells, 24(4), 986–991.

    Article  PubMed  CAS  Google Scholar 

  26. Mukherjee, S., Raje, N., Schoonmaker, J. A., Liu, J. C., Hideshima, T., Wein, M. N., et al. (2008). Pharmacologic targeting of a stem/progenitor population in vivo is associated with enhanced bone regeneration in mice. Journal of Clinical Investigation, 118(2), 491–504.

    PubMed  CAS  Google Scholar 

  27. Hong, J. H., Hwang, E. S., McManus, M. T., Amsterdam, A., Tian, Y., Kalmukova, R., et al. (2005). TAZ, a transcriptional modulator of mesenchymal stem cell differentiation. Science, 309(5737), 1074–1078.

    Article  PubMed  CAS  Google Scholar 

  28. von Metzler, I., Krebbel, H., Hecht, M., Manz, R. A., Fleissner, C., Mieth, M., et al. (2007). Bortezomib inhibits human osteoclastogenesis. Leukemia, 21(9), 2025–2034.

    Article  CAS  Google Scholar 

  29. Kim, C. H., & Broxmeyer, H. E. (1998). In vitro behavior of hematopoietic progenitor cells under the influence of chemoattractants: Stromal cell-derived factor-1, steel factor, and the bone marrow environment. Blood, 91(1), 100–110.

    PubMed  CAS  Google Scholar 

  30. Hideshima, T., Bergsagel, P. L., Kuehl, W. M., & Anderson, K. C. (2004). Advances in biology of multiple myeloma: Clinical applications. Blood, 104(3), 607–618.

    Article  PubMed  CAS  Google Scholar 

  31. Garrido, S. M., Appelbaum, F. R., Willman, C. L., & Banker, D. E. (2001). Acute myeloid leukemia cells are protected from spontaneous and drug-induced apoptosis by direct contact with a human bone marrow stromal cell line (HS-5). Experimental Hematology, 29(4), 448–457.

    Article  PubMed  CAS  Google Scholar 

  32. Burger, J. A., & Kipps, T. J. (2006). CXCR4: A key receptor in the crosstalk between tumor cells and their microenvironment. Blood, 107(5), 1761–1767.

    Article  PubMed  CAS  Google Scholar 

  33. Geay, J. F., Buet, D., Zhang, Y., Foudi, A., Jarrier, P., Berthebaud, M., et al. (2005). p210BCR-ABL inhibits SDF-1 chemotactic response via alteration of CXCR4 signaling and down-regulation of CXCR4 expression. Cancer Research, 65(7), 2676–2683.

    Article  PubMed  CAS  Google Scholar 

  34. Jin, L., Tabe, Y., Konoplev, S., Xu, Y., Leysath, C. E., Lu, H., et al. (2008). CXCR4 up-regulation by imatinib induces chronic myelogenous leukemia (CML) cell migration to bone marrow stroma and promotes survival of quiescent CML cells. Molecular Cancer Therapeutics, 7(1), 48–58.

    Article  PubMed  CAS  Google Scholar 

  35. Iwamoto, S., Mihara, K., Downing, J. R., Pui, C. H., & Campana, D. (2007). Mesenchymal cells regulate the response of acute lymphoblastic leukemia cells to asparaginase. Journal of Clinical Investigation, 117(4), 1049–1057.

    Article  PubMed  CAS  Google Scholar 

  36. Oettgen, H. F., Old, L. J., Boyse, E. A., Campbell, H. A., Philips, F. S., Clarkson, B. D., et al. (1967). Inhibition of leukemias in man by L-asparaginase. Cancer Research, 27(12), 2619–2631.

    PubMed  CAS  Google Scholar 

  37. Le Blanc, K., Rasmusson, I., Sundberg, B., Gotherstrom, C., Hassan, M., Uzunel, M., et al. (2004). Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet, 363(9419), 1439–1441.

    Article  PubMed  Google Scholar 

  38. Ning, H., Yang, F., Jiang, M., Hu, L., Feng, K., Zhang, J., et al. (2008). The correlation between cotransplantation of mesenchymal stem cells and higher recurrence rate in hematologic malignancy patients: Outcome of a pilot clinical study. Leukemia, 22(3), 593–599.

    Article  PubMed  CAS  Google Scholar 

  39. Rubio, D., Garcia-Castro, J., Martin, M. C., de la Fuente, R., Cigudosa, J. C., Lloyd, A. C., et al. (2005). Spontaneous human adult stem cell transformation. Cancer Research, 65(8), 3035–3039.

    PubMed  CAS  Google Scholar 

  40. Li, H., Fan, X., Kovi, R. C., Jo, Y., Moquin, B., Konz, R., et al. (2007). Spontaneous expression of embryonic factors and p53 point mutations in aged mesenchymal stem cells: A model of age-related tumorigenesis in mice. Cancer Research, 67(22), 10889–10898.

    Article  PubMed  CAS  Google Scholar 

  41. Rubio, D., Garcia, S., De la Cueva, T., Paz, M. F., Lloyd, A. C., Bernad, A., et al. (2008). Human mesenchymal stem cell transformation is associated with a mesenchymal-epithelial transition. Experimental Cell Research, 314(4), 691–698.

    Article  PubMed  CAS  Google Scholar 

  42. Houghton, J., Stoicov, C., Nomura, S., Rogers, A. B., Carlson, J., Li, H., et al. (2004). Gastric cancer originating from bone marrow-derived cells. Science, 306(5701), 1568–1571.

    Article  PubMed  CAS  Google Scholar 

  43. Bernardo, M. E., Zaffaroni, N., Novara, F., Cometa, A. M., Avanzini, M. A., Moretta, A., et al. (2007). Human bone marrow derived mesenchymal stem cells do not undergo transformation after long-term in vitro culture and do not exhibit telomere maintenance mechanisms. Cancer Research, 67(19), 9142–9149 Oct 1.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

J.S. is supported by a post-doctoral fellowship from the Canadian Institutes of Health Research.

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Correspondence to John Stagg.

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Stagg, J. Mesenchymal Stem Cells in Cancer. Stem Cell Rev 4, 119–124 (2008). https://doi.org/10.1007/s12015-008-9030-4

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