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Cancer Stem Cells and Metastasis: Emerging Themes and Therapeutic Implications

  • Leah Owens
  • Benjamin Tiede
  • Yibin Kang
Chapter

Abstract

Recent work in the field of cancer research has provided mounting evidence for the role of cancer stem cells in the establishment of many types of tumors. Insights into intrinsic properties of cancer stem cells are especially important in the context of tumor invasion and metastasis. Although more research is still necessary to solidify the role of cancer stem cells in the initiation of metastatic growth, the multistep cascade of tumor growth and progression as it is currently understood encompasses events likely to involve cancer stem cells and the microenvironment that supports them. This chapter will focus on the perceived roles of cancer stem cells in known tumorigenic and metastatic events. Emerging and evolving models of cancer stem cell-mediated tumor progression provide potential windows of opportunity for developing novel therapeutic strategies aiming at thwarting the menacing power of metastatic cancer stem cells.

Keywords

Stem Cell Vascular Endothelial Growth Factor Cancer Stem Cell Adult Stem Cell Stem Cell Niche 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Abraham, B., Fritz, P., McClellan, M., et al. 2005. Prevalence of CD44+/CS24-/low cells in breast cancer may not be associated with clinical outcome but may favor distant metastasis. Clinical Cancer Research 11: 1154–1159.PubMedGoogle Scholar
  2. Adams, G., Chabner, K., Alley, I., et al. 2006. Stem cell engraftment at the endosteal niche is specified by the calcium-sensing receptor. Nature 439: 599–603.PubMedCrossRefGoogle Scholar
  3. Al-Hajj, M., Wicha, M., Benito-Hernandez, A., Morrison, S., and Clarke, M. 2003. Prospective identification of tumorigenic breast cancer cells. Proceedings of the National Academy of Science USA 100: 3983–3988.CrossRefGoogle Scholar
  4. Bachoo, R., Maher, E., Ligon, K., Sharpless, N., Chan, S., et al. 2002. Epidermal growth factor receptor and Ink4a/Arf: convergent mechanisms governing terminal differentiation and transformation along the neural stem cell to astrocyte axis. Cancer Cell 1: 269–277.PubMedCrossRefGoogle Scholar
  5. Balic, M., Lin, H., Young, L., 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.PubMedCrossRefGoogle Scholar
  6. Bao, S., Wu, Q., McLendon, R., Hao, Y., Shi, Q., et al. 2006a. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 444: 756–760.PubMedCrossRefGoogle Scholar
  7. Bao, S., Wu, Q., Sathornumetee, S., Hao, Y., Li, Z., et al. 2006b. Stem cell-like glioma cells promote tumor angiogenesis through vascular endothelial factor. Cancer Research 66: 7843–7848.PubMedCrossRefGoogle Scholar
  8. Barnhart, B. and Simon, M. 2007. Metastasis and stem cell pathways. Cancer Metastasis Review 26: 261–271.CrossRefGoogle Scholar
  9. Bernards, R. and Weinberg, R.A. 2002. A progression puzzle. Nature 418 (6900): 823.PubMedCrossRefGoogle Scholar
  10. Brabletz, T., Jung, A., Reu, S., et al. 2001. Variable B-catenin expression in colorectal cancers indicates tumor progression driven by the tumor environment. Proceedings of the National Academy of Science USA 98: 10356–10361.CrossRefGoogle Scholar
  11. Cairns, J. 2002. Somatic stem cells and the kinetics of mutagenesis and carcinogenesis. Proceedings of the National Academy of Science USA 99: 10567–10570.CrossRefGoogle Scholar
  12. Calvi, L., Adams, G., Weibrecht, K., et al. 2003. Osteoblastic cells regulate the haematopoietic stem cell niche. Nature 425: 841–846.PubMedCrossRefGoogle Scholar
  13. Chambers, A.F., Groom, A.C., and MacDonald, I.C. 2002. Dissemination and growth of cancer cells in metastatic sites. Nature Reviews 2 (8): 563–572.PubMedCrossRefGoogle Scholar
  14. Chen, L., Shen, R., Ye, Y., Pu, X., Liu, X., et al. 2007. Precancerous stem cells have the potential for both benign and malignant differentiation. PLoS ONE 22: e293.CrossRefGoogle Scholar
  15. Desai, K., Xiao, N., Wang, W., Gangi, L., Greene, J., et al. 2002. Initiating oncogenic event determines gene-expression patterns of human breast cancer models. Proceedings of the National Academy of Science USA 99: 6967–6972.CrossRefGoogle Scholar
  16. Eriksson, M., Guse, K., Bauerschmitz, G., Virkkunen, P., Tarkkanen, M., et al. 2007. Oncolytic adenoviruses kill breast cancer initiating CD44(+)CD24(-/low) cells. Molecular Therapy 12: 2060–2061.Google Scholar
  17. Fidler, I. and Talmadge, J. 1986. Evidence that intravenously derived murine pulmonary melanoma metastases can originate from the expansion of a single tumor cell. Cancer Research 46: 5167–5171.PubMedGoogle Scholar
  18. Furger, K., Menon, R., Tuck, A., Bramwell, V., and Chambers, A. 2001. The functional and clinical roles of osteopontin in cancer and metastasis. Current Molecular Medicine 1: 621–632.PubMedCrossRefGoogle Scholar
  19. Gotzmann, J., Fischer, A.N.M., Zojer, M., Mikula, M., Proell, V., Huber, H., Jechlinger, M., Waerner, T., Weith, A., Beug, H., and Mikulits, W. 2006. A crucial function of PDGF in TGF-B-mediated cancer progression of hepatocytes. Oncogene 25: 3170–3185.PubMedCrossRefGoogle Scholar
  20. Guise, T., Mohammad, K., Clines, G., Stebbins, E., Wong, D., et al. 2006. Basic mechanisms responsible for osteolytic and osteoblastic bone metastases. Clinical Cancer Research 12: 6213s–6216s.CrossRefGoogle Scholar
  21. Gupta, G. and Massague, J. 2006. Cancer metastasis: building a framework. Cell 127: 679–695.PubMedCrossRefGoogle Scholar
  22. Hanahan, D. and Weinberg, R. 2000. The hallmarks of cancer. Cell 100: 57–70.PubMedCrossRefGoogle Scholar
  23. Hermann, P., Huber, S., Herrier, T., Aicher, A., Ellwart, J., et al. 2007. Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell 1: 313–323.PubMedCrossRefGoogle Scholar
  24. Hermann, P., Huber, S., and Heeschen, C. 2008. Metastatic cancer stem cells: a new target for anti-cancer therapy? Cell Cycle 7: 188–193.PubMedCrossRefGoogle Scholar
  25. Hiratsuka, S., Watanabe, A., Aburatani, J., and Maru, Y. 2006. Tumour-mediated upregulation of chemoattractants and recruitment of myeloid cells predetermines lung metastasis. Nature Cell Biology 8: 1369–1375.PubMedCrossRefGoogle Scholar
  26. Ho, M., Ng, A., Lam, S., and Hung, J. 2007. Side population in human lung cancer cell lines and tumors is enriched with stem-like cancer cells. Cancer Research 67: 4827–4833.PubMedCrossRefGoogle Scholar
  27. Hu, G., Chong, R.A., Yang, Q., Wei, Y., Blanco, M.A., Li, F., Reiss, M., Au, J.L., Haffy, B., and Kang, Y. 2009. MTDH activation by 8q22 genomic gain promotes chemoresistance and metastasis of poor-prognosis breast cancer. Cancer Cell 15: 9–20.Google Scholar
  28. Hurwitz, J., Fehrenbacher, L., Novonty, W., Cartwright, T., Hainsworth, J., Heim, W., Berlin, J., Baron, A., Griffing, S., Holmgren, E., Ferrara, N., Fyfe, G., Rogers, B., Ross, R., and Kabbinavar, F. 2004. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. New England Journal of Medicine 350: 2335–2342.PubMedCrossRefGoogle Scholar
  29. Hynes, R. 2003. Metastatic potential: generic predisposition of the primary tumor or rare, metastatic variants—or both? Cell 113: 821–823.PubMedCrossRefGoogle Scholar
  30. Ince, T., Richardson, A., Bell, G., Saitoh, M., Godar, S., et al. 2007. Transformation of different human breast epithelial cell types leads to distinct tumor phenotypes. Cancer Cell 12: 160–170.PubMedCrossRefGoogle Scholar
  31. Ito, M., Yang, Z., Andl, T., Cui, C., Kim, N., et al. 2007. Wnt-dependant de novo hair follicle regeneration in adult mouse skin after wounding. Nature 447: 316–320.PubMedCrossRefGoogle Scholar
  32. Jain, R. 2001. Normalizing tumor vasculature with anti-angiogenic therapy: a new paradigm for combination therapy. Nature Medicine 7: 987–989.PubMedCrossRefGoogle Scholar
  33. Jamieson, C., Ailles, L., Dylla, S., Muijtjens, M., Jones, C., et al. 2004. Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis CML. New England Journal of Medicine 351: 657–667.PubMedCrossRefGoogle Scholar
  34. Jemal, A., Siegel, R., Ward, W., Murray, T., Xu, J., et al. 2007. Cancer statistics, 2007. CA Cancer Journal of Clinicians 57: 43–66.CrossRefGoogle Scholar
  35. Jin, L., Hope, K., Zhai, Q., Smadja-Joffe, F., and Dick, J. 2006. Targeting of CD44 eradicates human acute myeloid leukemic stem cells. Nature Medicine 12: 1167–1174.PubMedCrossRefGoogle Scholar
  36. Kang, Y. 2005. Functional genomic analysis of cancer metastasis: biologic insights and clinical implications. Expert Review of Molecular Diagnostics 5 (3): 385–395.PubMedCrossRefGoogle Scholar
  37. Kang, Y., Siegel, R., Shu, W., Drobnjak, M., Kakonen, S., et al. 2003. A multigenic program mediating breast cancer metastasis to bone. Cancer Cell 3: 537–549.PubMedCrossRefGoogle Scholar
  38. Kaplan, R., Riba, R., Zacharoulis, S., Bramley, A., Vincent, L., et al. 2005. VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature 438: 820–827.PubMedCrossRefGoogle Scholar
  39. Kim, C., Kackson, E., Woolfenden, A., et al. 2005. Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell 121: 823–835.PubMedCrossRefGoogle Scholar
  40. Kollet, O., Dar, A., Shivtiel, S., Kalinkovixh, A., Lapid, K., et al. 2006. Osteoclasts degrade endosteal components and promote mobilizations of hematopoietic progenitor cells. Nature Medicine 12: 657–664.PubMedCrossRefGoogle Scholar
  41. Krause, D., Lazarides, K., van Andrian, U., and van Etten, R. 2006. Requirement for CD44 in homing and engraftment of BCR-ABL-expressing leukemic stem cells. Nature Medicine 12: 1175–1180.PubMedCrossRefGoogle Scholar
  42. Krivtsov, A., Twomey, D., Feng, Z., Stubbs, M., Wang, Y., et al. 2006. Transformation from committed progenitor to leukaemia stem cell initiated by MLL-AF9. Nature 442: 821–822.CrossRefGoogle Scholar
  43. Li, L. and Neaves, W. 2006. Normal stem cells and cancer stem cells: the niche matters. Cancer Research 66: 4553–4557.PubMedCrossRefGoogle Scholar
  44. Li, F., Tiede, B., Massague, J., and Kang, Y. 2006. Beyond tumorigenesis: cancer stem cells in metastasis. Cell Research 17: 3–14.CrossRefGoogle Scholar
  45. Lin, M. and Sessa, W. 2004. Antiangiogenic therapy: creating a unique "window" of opportunity. Cancer Cell 6: 529–531.PubMedGoogle Scholar
  46. Ma, S., Lee, T., Zheng, B., Chan, K., and Guan, X. 2008. CD133(+) HCC cancer stem cells confer chemoresistance by preferential expression of the Akt/PKB survival pathway. Oncogene 27: 1749–1758.PubMedCrossRefGoogle Scholar
  47. Mihai, R., Stevens, J., McKinney, C., and Ibrahim, N.B. 2006. Expression of the calcium receptor in human breast cancer—a potential new marker predicting the risk of bone metastases. European Journal of Surgical Oncology 32 (5): 511–515.PubMedCrossRefGoogle Scholar
  48. Minn, A.J., Gupta, G.P., Siegel, P.M., et al. 2005a. Genes that mediate breast cancer metastasis to lung. Nature 436: 518–524.PubMedCrossRefGoogle Scholar
  49. Minn, A.J., Kang, Y., Serganova, I., Gupta, G.P., Giri, D., Doubrovin, M., Ponomarev, V., Gerald, W., Blasberg, R., and Massague, J. 2005b. Distinct organ-specific metastatic potential of individual breast cancer cells and primary tumors. The Journal of Clinical Investigation 115: 44–55.PubMedGoogle Scholar
  50. Miyamoto, T., Weissman, I., and Akashi, K. 2000. AML1/ETO-expressing nonleukemic stem cells in acute myelogenous leukemia with 8:21 chromosomal translocation. Proceedings of the National Academy of Science USA 97: 7521–7526.CrossRefGoogle Scholar
  51. Muller, A., Homey, B., Soto, H., Ge, N., Catron, D., Buchanan, M.E., McClanahan, T., Murphy, E., Yuan, W., Wagner, S.N., Barrera, J.L., Mohar, A., Verastegui, E., and Zlotnik, A. 2001. Involvement of chemokine receptors in breast cancer metastasis. Nature 410 (6824): 50–56.PubMedCrossRefGoogle Scholar
  52. Paget, S. 1989. The distribution of secondary growths in cancer of the breast. 1889. Cancer Metastasis Reviews 8 (2): 98–101.PubMedGoogle Scholar
  53. Perou, C., Jeffrey, S., Van De Rinj, M., Rees, C., Wisen, M., et al. 1999. Distinctive gene expression patterns in human mammary epithelial cells and breast cancers. Proceedings of the National Academy of Science USA 2002: 9212–9217.CrossRefGoogle Scholar
  54. Phillips, T., McBride, W., and Pajonk, F. 2006. The response of CD24(-/low)/CD44+ breast cancer initiating cells to radiation. Journal of the National Cancer Institute 98: 1777–1785.PubMedCrossRefGoogle Scholar
  55. Piccirillo, S., Reynolds, B., Zanetti, N., et al. 2006. Bone morphogenic proteins inhibit the tumorigenic potential of human brain tumour-initiating cells. Nature 444: 761–765.PubMedCrossRefGoogle Scholar
  56. Ramaswamy, S., Ross, K., Lander, E., and Golub, T. 2003. A molecular signature of metastasis in primary solid tumors. Nature Genetics 33: 49–54.PubMedCrossRefGoogle Scholar
  57. Scadden, D. 2006. The stem-cell niche as an entity of action. Nature 441: 1075–1079.PubMedCrossRefGoogle Scholar
  58. Scheel, C., Onder, T., Karnoub, A., and Weinberg, R. 2007. Adaptation versus selection: the origins of metastatic behavior. Cancer Research 67: 11476–11479.PubMedCrossRefGoogle Scholar
  59. Schofield, R. 1978. The relationship between the spleen colony-forming cell and the haemopoietic stem cell. Blood Cells 4: 7–25.PubMedGoogle Scholar
  60. Shackelton, M., Vaillant, F., Simpson, K., Stingl, J., Smyth, G., et al. 2006. Generation of a functional mammary gland from a single stem cell. Nature 439: 84–88.CrossRefGoogle Scholar
  61. Sheridan, C., Kishimoto, H., Fuchs, R., Mehrotra, S., Bhat-Nakshatri, P., et al. 2006. CD44+/CD24- breast cancer cells exhibit enhanced invasive properties: an early step necessary for metastasis. Cancer Research 8: R59.Google Scholar
  62. Shipitsin, M., Campbell, L., Argani, P., Weremowicz, S., Bloushtain-Qimron, N., et al. 2007. Molecular definition of breast tumor heterogeneity. Cancer Cell 11: 259–273.PubMedCrossRefGoogle Scholar
  63. Sleeman, J. and Cremers, N. 2007. New concepts in breast cancer metastasis: tumor initiating cells and the microenvironment. Clinical & Experimental Metastasis 24: 707–715.CrossRefGoogle Scholar
  64. Sneddon, J., Zhen, H., Montgomery, K., et al. 2006. Bone morphogenetic protein antagonist gremlin1 is widely expressed by cancer-associated stromal cells and can promote tumor cell proliferation. Proceedings of the National Academy of Science USA 103: 14842–14847.CrossRefGoogle Scholar
  65. Sorlie, T., Perou, C., Tibshirani, R., Aas, T., Geisler, S., et al. 2001. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proceedings of the National Academy of Science USA 98: 10869–10874.CrossRefGoogle Scholar
  66. Steeg, P.S. 2006. Tumor metastasis: mechanistic insights and clinical challenges. Nature Medicine 12 (8): 895–904.PubMedCrossRefGoogle Scholar
  67. Stier, S., Ko, Y., Forkert, R., et al. 2005. Osteopontin is a hematopoietic stem cell niche component that negatively regulates stem cell pool size. Journal of Experimental Medicine 201: 1781–1791.PubMedCrossRefGoogle Scholar
  68. Stingl, J. and Caldas, C. 2007. Molecular heterogeneity of breast carcinomas and the cancer stem cell hypothesis. Nature Review Cancer 7: 791–799.Google Scholar
  69. Taichman, R.S., Cooper, C., Keller, E.T., Pienta, K.J., Taichman, N.S., and McCauley, L.K. 2002. Use of the stromal cell-derived factor-1/CXCR4 pathway in prostate cancer metastasis to bone. Cancer Research 62 (6): 1832–1837.PubMedGoogle Scholar
  70. Tavor, S., Petit, I., Porozov, S., Avigdor, A., Dar, A., et al. 2004. CXCR4 regulates migration and development of human acute myelogenous leukemia stem cells in transplanted NOD/SCID mice. Cancer Research 64: 2817–2824.PubMedCrossRefGoogle Scholar
  71. Turhan, A., Lemoine, F., Debert, C., Bonnet, M., Baillou, C., et al. 1995. Highly purified primitive hematopoietic stem cells are PML-RARA negative and generate nonclonal progenitors in acute promyelocytic leukemia. Blood 85: 2154–2161.PubMedGoogle Scholar
  72. van de Vijver, M., He, Y., van't Veer, L., Dai, H., Hart, A., et al. 2002. A gene-expression signature as a predictor of survival in breast cancer. New England Journal of Medicine 347: 1999–2009.PubMedCrossRefGoogle Scholar
  73. van't Veer, L., Dai, H., van de Vijver, M., He, Y., Hart, A., et al. 2002. Gene expression profiling predicts clinical outcome of breast cancer. Nature 415: 530–536.CrossRefGoogle Scholar
  74. Vescovi, A., Galli, R., and Reynolds, B. 2006. Brain tumour stem cells. Nature Review Cancer 6: 425–436.CrossRefGoogle Scholar
  75. Wang, Y., Klijn, J., Zhang, Y., Sieuwerts, A., Look, M., et al. 2005. Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer. Lancet 365: 671–679.PubMedGoogle Scholar
  76. Weigelt, B., Hu, Z., He, X., et al. 2005a. Molecular portraits and 70-gene prognosis signature are preserved throughout the metastatic process of breast cancer. Cancer Research 65: 9155–9158.PubMedCrossRefGoogle Scholar
  77. Weigelt, B., Peterse, J.L., and van 't Veer, L.J. 2005b. Breast cancer metastasis: markers and models. Nature Reviews Cancer 5 (8): 591–602.PubMedCrossRefGoogle Scholar
  78. Wernig, M., Meissner, A., Foreman, R., et al. 2007. In vitro reprogramming of fibroblasts into pluripotent ES-cell-like state. Nature 448: 318–324.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Department of Molecular BiologyPrinceton UniversityPrincetonUSA

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