Advertisement

Stem Cell Reviews

, Volume 4, Issue 2, pp 119–124 | Cite as

Mesenchymal Stem Cells in Cancer

  • John StaggEmail author
Article

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.

Keywords

Mesenchymal stem cells MSC Cancer Stromal cells Stroma Carcinoma-associated fibroblasts CAF GvHD 

Notes

Acknowledgments

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

References

  1. 1.
    Stagg, J. (2007). Immune regulation by mesenchymal stem cells: Two sides to the coin. Tissue Antigens, 69(1), 1–9.PubMedCrossRefGoogle Scholar
  2. 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.PubMedCrossRefGoogle Scholar
  3. 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.PubMedCrossRefGoogle Scholar
  4. 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.PubMedCrossRefGoogle Scholar
  5. 5.
    Massague, J., Blain, S. W., & Lo, R. S. (2000). TGFbeta signaling in growth control, cancer, and heritable disorders. Cell, 103(2), 295–309.PubMedCrossRefGoogle Scholar
  6. 6.
    Mishra, L., Derynck, R., & Mishra, B. (2005). Transforming growth factor-beta signaling in stem cells and cancer. Science, 310(5745), 68–71.PubMedCrossRefGoogle Scholar
  7. 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.PubMedCrossRefGoogle Scholar
  8. 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.PubMedCrossRefGoogle Scholar
  9. 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.PubMedCrossRefGoogle Scholar
  10. 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.PubMedGoogle Scholar
  11. 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.PubMedCrossRefGoogle Scholar
  12. 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.PubMedCrossRefGoogle Scholar
  13. 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.PubMedCrossRefGoogle Scholar
  14. 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.PubMedGoogle Scholar
  15. 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.PubMedCrossRefGoogle Scholar
  16. 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.PubMedCrossRefGoogle Scholar
  17. 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.CrossRefGoogle Scholar
  18. 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.PubMedCrossRefGoogle Scholar
  19. 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.PubMedCrossRefGoogle Scholar
  20. 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.PubMedCrossRefGoogle Scholar
  21. 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.Google Scholar
  22. 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.PubMedCrossRefGoogle Scholar
  23. 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.PubMedCrossRefGoogle Scholar
  24. 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.PubMedCrossRefGoogle Scholar
  25. 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.PubMedCrossRefGoogle Scholar
  26. 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.PubMedGoogle Scholar
  27. 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.PubMedCrossRefGoogle Scholar
  28. 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.CrossRefGoogle Scholar
  29. 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.PubMedGoogle Scholar
  30. 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.PubMedCrossRefGoogle Scholar
  31. 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.PubMedCrossRefGoogle Scholar
  32. 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.PubMedCrossRefGoogle Scholar
  33. 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.PubMedCrossRefGoogle Scholar
  34. 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.PubMedCrossRefGoogle Scholar
  35. 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.PubMedCrossRefGoogle Scholar
  36. 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.PubMedGoogle Scholar
  37. 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.PubMedCrossRefGoogle Scholar
  38. 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.PubMedCrossRefGoogle Scholar
  39. 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.PubMedGoogle Scholar
  40. 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.PubMedCrossRefGoogle Scholar
  41. 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.PubMedCrossRefGoogle Scholar
  42. 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.PubMedCrossRefGoogle Scholar
  43. 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.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press 2008

Authors and Affiliations

  1. 1.Cancer Immunology Program, Trescowthick LaboratoriesPeter MacCallum Cancer CentreEast MelbourneAustralia

Personalised recommendations