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Stem Cells and Cancer: An Overview

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Abstract

Definite evidence of the importance of cancer stem cells in the progression of cancer has now come to light. Key markers of these cells have been identified in many solid tumours as well as leukaemias. Specific studies modelling the tumour induction of specific cells isolated by surface antigens such as CD44 have demonstrated that these cells are not only present in tumours but that they are the key units in their tumourgenecity. These findings provide useful insight for disease progression, treatment and metastasis. The wide variety of proposed markers, and their similarity to endothelial progenitor cells found in angiogenesis, complicates these studies. Definite proof falls only in the induction of tumours in vivo. Here we review the developments in cancer stem cells and the markers that have been found for these cells.

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References

  1. Hatfield, S. D., Shcherbata, H. R., Fischer, K. A., Nakahara, K., Carthew, R. W., & Ruohola-Baker, H. (2005). Stem cell division is regulated by the microRNA pathway. Nature, 435, 974–978.

    Article  PubMed  CAS  Google Scholar 

  2. Jiang, Y., Jahagirdar, B. N., Reinhardt, R. L., Schwartz, R. E., Keene, C. D., Ortiz-Gonzalez, X. R., et al. (2002). Pluripotency of mesenchymal stem cells derived from adult marrow. Nature, 418, 41–49.

    Article  PubMed  CAS  Google Scholar 

  3. Kim, C. F., Jackson, E. L., Woolfenden, A. E., Lawrence, S., Babar, I., Vogel, S., et al. (2005). Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell, 121, 823–835.

    Article  PubMed  CAS  Google Scholar 

  4. Simonsen, J. L., Rosada, C., Serakinci, N., Justesen, J., Stenderup, K., Rattan, S. I., et al. (2002). Telomerase expression extends the proliferative life-span and maintains the osteogenic potential of human bone marrow stromal cells. Nature Biotechnology, 20, 592–596.

    Article  PubMed  CAS  Google Scholar 

  5. Dick, J. E. (2003). Breast cancer stem cells revealed. Proceedings of the National Academy of Sciences of the United States of America, 100, 3547–3549.

    Article  PubMed  CAS  Google Scholar 

  6. Reya, T., Morrison, S. J., Clarke, M. F., & Weissman, I. L. (2001). Stem cells, cancer, and cancer stem cells. Nature, 414, 105–111.

    Article  PubMed  CAS  Google Scholar 

  7. Park, C. H., Bergsagel, D. E., & McCulloch, E. A. (1971). Mouse myeloma tumor stem cells: A primary cell culture assay. Journal of the National Cancer Institute, 46, 411–422.

    PubMed  CAS  Google Scholar 

  8. Bonnet, D., & Dick, J. E. (1997). Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Natural Medicines, 3, 730–737.

    Article  CAS  Google Scholar 

  9. Al Hajj, M., Wicha, M. S., Benito-Hernandez, A., Morrison, S. J., & Clarke, M. F. (2003). Prospective identification of tumorigenic breast cancer cells. Proceedings of the National Academy of Sciences of the United States of America, 100, 3983–3988.

    Article  PubMed  CAS  Google Scholar 

  10. Chiba, T., Kita, K., Zheng, Y. W., Yokosuka, O., Saisho, H., Iwama, A., et al. (2006). Side population purified from hepatocellular carcinoma cells harbors cancer stem cell-like properties. Hepatology, 44, 240–251.

    Article  PubMed  CAS  Google Scholar 

  11. Balic, M., Lin, H., Young, L., Hawes, D., Giuliano, A., McNamara, G., et al. (2006). Most early disseminated cancer cells detected in bone marrow of breast cancer patients have a putative breast cancer stem cell phenotype. Clinical Cancer Research, 12, 5615–5621.

    Article  PubMed  CAS  Google Scholar 

  12. Kruger, J. A., Kaplan, C. D., Luo, Y., Zhou, H., Markowitz, D., Xiang, R., et al. (2006). Characterization of stem cell-like cancer cells in immune-competent mice. Blood, 108, 3906–3912.

    Article  PubMed  CAS  Google Scholar 

  13. Knudson Jr., A. G., Strong, L. C., & Anderson, D. E. (1973). Heredity and cancer in man. Progress in Medical Genetics, 9, 113–158.

    PubMed  Google Scholar 

  14. Morrison, S. J., Qian, D., Jerabek, L., Thiel, B. A., Park, I. K., Ford, P. S., et al. (2002). A genetic determinant that specifically regulates the frequency of hematopoietic stem cells. Journal of Immunology, 168, 635–642.

    CAS  Google Scholar 

  15. Al Hajj, M., Becker, M. W., Wicha, M., Weissman, I., & Clarke, M. F. (2004). Therapeutic implications of cancer stem cells. Current Opinion in Genetics and Development, 14, 43–47.

    Article  PubMed  CAS  Google Scholar 

  16. Wang, J. C., & Dick, J. E. (2005). Cancer stem cells: Lessons from leukemia. Trends in Cell Biology, 15, 494–501.

    Article  PubMed  CAS  Google Scholar 

  17. Cozzio, A., Passegue, E., Ayton, P. M., Karsunky, H., Cleary, M. L., & Weissman, I. L. (2003). Similar MLL-associated leukemias arising from self-renewing stem cells and short-lived myeloid progenitors. Genes & Development, 17, 3029–3035.

    Article  CAS  Google Scholar 

  18. Weissman, I. L. (2005). Normal and neoplastic stem cells. Novartis Foundation Symposium, 265, 35–50.

    PubMed  Google Scholar 

  19. Jamieson, C. H., Ailles, L. E., Dylla, S. J., Muijtjens, M., Jones, C., Zehnder, J. L., et al. (2004). Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis CML. New England Journal of Medicine, 351, 657–667.

    Article  PubMed  CAS  Google Scholar 

  20. Galli, R., Binda, E., Orfanelli, U., Cipelletti, B., Gritti, A., De Vitis, S., et al. (2004). Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma. Cancer Research, 64, 7011–7021.

    Article  PubMed  CAS  Google Scholar 

  21. Yuan, X., Curtin, J., Xiong, Y., Liu, G., Waschsmann-Hogiu, S., Farkas, D. L., et al. (2004). Isolation of cancer stem cells from adult glioblastoma multiforme. Oncogene, 23, 9392–9400.

    Article  PubMed  CAS  Google Scholar 

  22. Singh, S. K., Hawkins, C., Clarke, I. D., Squire, J. A., Bayani, J., Hide, T., et al. (2004). Identification of human brain tumour initiating cells. Nature, 432, 396–401.

    Article  PubMed  CAS  Google Scholar 

  23. Xin, L., Lawson, D. A., & Witte, O. N. (2005). The Sca-1 cell surface marker enriches for a prostate-regenerating cell subpopulation that can initiate prostate tumorigenesis. Proceedings of the National Academy of Sciences of the United States of America, 102, 6942–6947.

    Article  PubMed  CAS  Google Scholar 

  24. Stockler, M., Wilcken, N. R., Ghersi, D., & Simes, R. J. (2000). Systematic reviews of chemotherapy and endocrine therapy in metastatic breast cancer. Cancer Treatment Reviews, 26, 151–168.

    Article  PubMed  CAS  Google Scholar 

  25. Lippman, M. E. (2000). High-dose chemotherapy plus autologous bone marrow transplantation for metastatic breast cancer. New England Journal of Medicine, 342, 1119–1120.

    Article  PubMed  CAS  Google Scholar 

  26. Groszer, M., Erickson, R., Scripture-Adams, D. D., Lesche, R., Trumpp, A., Zack, J. A., et al. (2001). Negative regulation of neural stem/progenitor cell proliferation by the Pten tumor suppressor gene in vivo. Science, 294, 2186–2189.

    Article  PubMed  CAS  Google Scholar 

  27. Park, I. K., Qian, D., Kiel, M., Becker, M. W., Pihalja, M., Weissman, I. L., et al. (2003). Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells. Nature, 423, 302–305.

    Article  PubMed  CAS  Google Scholar 

  28. Costello, R. T., Mallet, F., Gaugler, B., Sainty, D., Arnoulet, C., Gastaut, J. A., et al. (2000). Human acute myeloid leukemia CD34+/. Cancer Research, 60, 4403–4411.

    PubMed  CAS  Google Scholar 

  29. Guzman, M. L., Swiderski, C. F., Howard, D. S., Grimes, B. A., Rossi, R. M., Szilvassy, S. J., et al. (2002). Preferential induction of apoptosis for primary human leukemic stem cells. Proceedings of the National Academy of Sciences of the United States of America, 99, 16220–16225.

    Article  PubMed  CAS  Google Scholar 

  30. Blair, A., Hogge, D. E., Ailles, L. E., Lansdorp, P. M., & Sutherland, H. J. (1997). Lack of expression of Thy-1 (CD90) on acute myeloid leukemia cells with long-term proliferative ability in vitro and in vivo. Blood, 89, 3104–3112.

    PubMed  CAS  Google Scholar 

  31. Blair, A., & Sutherland, H. J. (2000). Primitive acute myeloid leukemia cells with long-term proliferative ability in vitro and in vivo lack surface expression of c-kit (CD117). Experimental Hematology, 28, 660–671.

    Article  PubMed  CAS  Google Scholar 

  32. Druker, B. J., Tamura, S., Buchdunger, E., Ohno, S., Segal, G. M., Fanning, S., et al. (1996). Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Natural Medicines, 2, 561–566.

    Article  CAS  Google Scholar 

  33. O’Brien, S. G., Guilhot, F., Larson, R. A., Gathmann, I., Baccarani, M., Cervantes, F., et al. (2003). Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. New England Journal of Medicine, 348, 994–1004.

    Article  PubMed  CAS  Google Scholar 

  34. Branford, S., Hughes, T. P., & Rudzki, Z. (1999). Monitoring chronic myeloid leukaemia therapy by real-time quantitative PCR in blood is a reliable alternative to bone marrow cytogenetics. British Journal of Haematology, 107, 587–599.

    Article  PubMed  CAS  Google Scholar 

  35. Berman, D. M., Karhadkar, S. S., Hallahan, A. R., Pritchard, J. I., Eberhart, C. G., Watkins, D. N., et al. (2002). Medulloblastoma growth inhibition by hedgehog pathway blockade. Science, 297, 1559–1561.

    Article  PubMed  CAS  Google Scholar 

  36. Beachy, P. A., Karhadkar, S. S., & Berman, D. M. (2004). Tissue repair and stem cell renewal in carcinogenesis. Nature, 432, 324–331.

    Article  PubMed  CAS  Google Scholar 

  37. Clement, V., Sanchez, P., de Tribolet, N., Radovanovic, I., & Altaba, A. (2007). HEDGEHOG-GLI1 signaling regulates human glioma growth, cancer stem cell self-renewal, and tumorigenicity. Current Biology, 17, 165–172.

    Article  PubMed  CAS  Google Scholar 

  38. Sagar, J., Chaib, B., Sales, K., Winslet, M., & Seifalian, A. (2007). Role of stem cells in cancer therapy and cancer stem cells: A review. Cancer Cell International, 7, 9.

    Article  PubMed  Google Scholar 

  39. Studeny, M., Marini, F. C., Champlin, R. E., Zompetta, C., Fidler, I. J., & Andreeff, M. (2002). Bone marrow-derived mesenchymal stem cells as vehicles for interferon-beta delivery into tumors. Cancer Research, 62, 3603–3608.

    PubMed  CAS  Google Scholar 

  40. Anderson, S. A., Glod, J., Arbab, A. S., Noel, M., Ashari, P., Fine, H. A., et al. (2005). Noninvasive MR imaging of magnetically labeled stem cells to directly identify neovasculature in a glioma model. Blood, 105, 420–425.

    Article  PubMed  CAS  Google Scholar 

  41. 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, 3307–3318.

    PubMed  CAS  Google Scholar 

  42. Chawla-Sarkar, M., Leaman, D. W., & Borden, E. C. (2001). Preferential induction of apoptosis by interferon (IFN)-beta compared with IFN-alpha2: Correlation with TRAIL/Apo2L induction in melanoma cell lines. Clinical Cancer Research, 7, 1821–1831.

    PubMed  CAS  Google Scholar 

  43. Atlasi, Y., Mowla, S. J., Ziaee, S. A., & Bahrami, A. R. (2007). OCT-4, an embryonic stem cell marker, is highly expressed in bladder cancer. International Journal of Cancer, 120, 1598–1602.

    Article  CAS  Google Scholar 

  44. Gibbs, C. P., Kukekov, V. G., Reith, J. D., Tchigrinova, O., Suslov, O. N., Scott, E. W., et al. (2005). Stem-like cells in bone sarcomas: Implications for tumorigenesis. Neoplasia, 7, 967–976.

    Article  PubMed  CAS  Google Scholar 

  45. Donnenberg, V. S., Landreneau R. J., & Donnenberg, A. D. (2007). Tumorigenic stem and progenitor cells: Implications for the therapeutic index of anti-cancer agents. Journal of Controlled Release, 122, 385–391.

    Google Scholar 

  46. Dalerba, P., Dylla, S. J., Park, I. K., Liu, R., Wang, X., Cho, R. W., et al. (2007). Phenotypic characterization of human colorectal cancer stem cells. Proceedings of the National Academy of Sciences of the United States of America, 104, 10158–10163.

    Article  PubMed  CAS  Google Scholar 

  47. Dontu, G., Liu, S., & Wicha, M. S. (2005). Stem cells in mammary development and carcinogenesis: Implications for prevention and treatment. Stem Cell Review, 1, 207–213.

    Article  CAS  Google Scholar 

  48. Liu, S., Dontu, G., Mantle, I. D., Patel, S., Ahn, N. S., Jackson, K. W., et al. (2006). Hedgehog signaling and Bmi-1 regulate self-renewal of normal and malignant human mammary stem cells. Cancer Research, 66, 6063–6071.

    Article  PubMed  CAS  Google Scholar 

  49. Tang, C., Chua, C. L., & Ang, B. T. (2007). Insights into the cancer stem cell model of glioma tumorigenesis. Annals of the Academy of Medicine, Singapore, 36, 352–356.

    PubMed  Google Scholar 

  50. Haraguchi, N., Inoue, H., Tanaka, F., Mimori, K., Utsunomiya, T., Sasaki, A., et al. (2006). Cancer stem cells in human gastrointestinal cancers. Human Cell, 19, 24–29.

    Article  PubMed  Google Scholar 

  51. Park, D. M., Li, J., Okamoto, H., Akeju, O., Kim, S. H., Lubensky, I., et al. (2007). N-CoR pathway targeting induces glioblastoma derived cancer stem cell differentiation. Cell Cycle, 6, 467–470.

    PubMed  CAS  Google Scholar 

  52. Kvinlaug, B. T., & Huntly, B. J. (2007). Targeting cancer stem cells. Expert Opinion on Therapeutic Targets, 11, 915–927.

    Article  PubMed  CAS  Google Scholar 

  53. Prince, M. E., Sivanandan, R., Kaczorowski, A., Wolf, G. T., Kaplan, M. J., Dalerba, P., et al. (2007). Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proceedings of the National Academy of Sciences of the United States of America, 104, 973–978.

    Article  PubMed  CAS  Google Scholar 

  54. Phatak, P., Cookson, J. C., Dai, F., Smith, V., Gartenhaus, R. B., Stevens, M. F., et al. (2007). Telomere uncapping by the G-quadruplex ligand RHPS4 inhibits clonogenic tumour cell growth in vitro and in vivo consistent with a cancer stem cell targeting mechanism. British Journal of Cancer, 96, 1223–1233.

    Article  PubMed  CAS  Google Scholar 

  55. Ishikawa, K., Sasaki, A., Haraguchi, N., Yoshikawa, Y., & Mori, M. (2007). A case of an alpha-fetoprotein-producing intrahepatic cholangiocarcinoma suggests probable cancer stem cell origin. Oncologist, 12, 320–324.

    Article  PubMed  CAS  Google Scholar 

  56. Sengupta, A., Banerjee, D., Chandra, S., Banerji, S. K., Ghosh, R., Roy, R., et al. (2007). Deregulation and cross talk among Sonic hedgehog, Wnt, Hox and Notch signaling in chronic myeloid leukemia progression. Leukemia, 21, 949–955.

    Article  PubMed  CAS  Google Scholar 

  57. Krivtsov, A. V., Twomey, D., Feng, Z., Stubbs, M. C., Wang, Y., Faber, J., et al. (2006). Transformation from committed progenitor to leukaemia stem cell initiated by MLL-AF9. Nature, 442, 818–822.

    Article  PubMed  CAS  Google Scholar 

  58. Nam, C. H., & Rabbitts, T. H. (2006). The role of LMO2 in development and in T cell leukemia after chromosomal translocation or retroviral insertion. Molecular Therapy, 13, 15–25.

    Article  PubMed  CAS  Google Scholar 

  59. Lam, W. K., & Watkins, D. N. (2007). Lung cancer: Future directions. Respirology, 12, 471–477.

    Article  PubMed  Google Scholar 

  60. Fang, D., Nguyen, T. K., Leishear, K., Finko, R., Kulp, A. N., Hotz, S., et al. (2005). A tumorigenic subpopulation with stem cell properties in melanomas. Cancer Research, 65, 9328–9337.

    Article  PubMed  CAS  Google Scholar 

  61. Peacock, C. D., Wang, Q., Gesell, G. S., Corcoran-Schwartz, I. M., Jones, E., Kim, J., et al. (2007). Hedgehog signaling maintains a tumor stem cell compartment in multiple myeloma. Proceedings of the National Academy of Sciences of the United States of America, 104, 4048–4053.

    Article  PubMed  CAS  Google Scholar 

  62. Panagiotakos, G., & Tabar, V. (2007). Brain tumor stem cells. Current Neurology and Neuroscience Reports, 7, 215–220.

    Article  PubMed  Google Scholar 

  63. Heffron, C. C., Gallagher, M. F., Guenther, S., Sherlock, J., Henfrey, R., Martin, C., et al. (2007). Global mRNA analysis to determine a transcriptome profile of cancer stemness in a mouse model. Anticancer Research, 27, 1319–1324.

    PubMed  CAS  Google Scholar 

  64. Wang, J., Guo, L. P., Chen, L. Z., Zeng, Y. X., & Lu, S. H. (2007). Identification of cancer stem cell-like side population cells in human nasopharyngeal carcinoma cell line. Cancer Research, 67, 3716–3724.

    Article  PubMed  CAS  Google Scholar 

  65. Collins, A. T., & Maitland, N. J. (2006). Prostate cancer stem cells. European Journal of Cancer, 42, 1213–1218.

    Article  PubMed  CAS  Google Scholar 

  66. Collins, A. T., Berry, P. A., Hyde, C., Stower, M. J., & Maitland, N. J. (2005). Prospective identification of tumorigenic prostate cancer stem cells. Cancer Research, 65, 10946–10951.

    Article  PubMed  CAS  Google Scholar 

  67. Rizzo, S., Attard, G., & Hudson, D. L. (2005). Prostate epithelial stem cells. Cell Proliferation, 38, 363–374.

    Article  PubMed  CAS  Google Scholar 

  68. Mohan, A., Kandalam, M., Ramkumar, H. L., Gopal, L., & Krishnakumar, S. (2006). Stem cell markers: ABCG2 and MCM2 expression in retinoblastoma. British Journal of Ophthalmology, 90, 889–893.

    Article  PubMed  CAS  Google Scholar 

  69. Seigel, G. M., Campbell, L. M., Narayan, M., & Gonzalez-Fernandez, F. (2005). Cancer stem cell characteristics in retinoblastoma. Molecular Vision, 11, 729–737.

    PubMed  CAS  Google Scholar 

  70. Gutova, M., Najbauer, J., Gevorgyan, A., Metz, M. Z., Weng, Y., Shih, C. C., et al. (2007). Identification of uPAR-positive Chemoresistant Cells in Small Cell Lung Cancer. PLoS ONE, 2, e243.

    Article  PubMed  Google Scholar 

  71. Diabira, S., & Morandi, X. (2007). Gliomagenesis and neural stem cells: Key role of hypoxia and concept of tumor “neo-niche.” Medical Hypotheses (in press).

  72. Zhang, P., Zuo, H., Ozaki, T., Nakagomi, N., & Kakudo, K. (2006). Cancer stem cell hypothesis in thyroid cancer. Pathology International, 56, 485–489.

    Article  PubMed  CAS  Google Scholar 

  73. Pascal, L. E., Oudes, A. J., Petersen, T. W., Goo, Y. A., Walashek, L. S., True, L. D., et al. (2007). Molecular and cellular characterization of ABCG2 in the prostate. BMC Urology, 7, 6.

    Article  PubMed  Google Scholar 

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Sales, K.M., Winslet, M.C. & Seifalian, A.M. Stem Cells and Cancer: An Overview. Stem Cell Rev 3, 249–255 (2007). https://doi.org/10.1007/s12015-007-9002-0

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