Tumor Biology

, Volume 31, Issue 4, pp 243–253 | Cite as

Emerging strategies for the identification and targeting of cancer stem cells

  • Jun Dou
  • Ning Gu
Research Article


The hypothesis of cancer stem cells (CSCs) is receiving increasing interest and has become the subject of considerable debate among cancer researchers. Recent rapid progress in CSC research has encountered increasing difficulties and challenges. Understanding the biologic characteristic of CSCs is crucial to start with better identification and diagnosis based on CSC markers and eventually targeting to CSCs will undoubtedly result in improved prevention and treatment of many types of CSCs. We discuss here some of the approaching strategies that include establishing special methods of identifying CSCs and targeting therapies of CSCs.


Cancer stem cells Challenge Strategy 



This work was supported by the Science Foundation of Southeast University (No. 9223001446), in part by the National Natural Science Foundation of China (No. 90406023), and in part by the 973 Program of China (No.2006CB933206). We also thank Dr. Lin Wang in Atlanta, GA, USA for kindly editing the manuscript.


  1. 1.
    Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA. 2003;100:3983–8.PubMedGoogle Scholar
  2. 2.
    Singh SK, Clarke ID, Terasaki M, et al. Identification of a cancer stem cell in human brain tumors. Cancer Res. 2003;63:5821–8.PubMedGoogle Scholar
  3. 3.
    Singh SK, Hawkins C, Clarke ID. Identification of human brain tumour initiating cells. Nature. 2004;432:396–401.PubMedGoogle Scholar
  4. 4.
    Pierce GB. Neoplasms, differentiations and mutations. Am J Pathol. 1974;77:103–18.PubMedGoogle Scholar
  5. 5.
    Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature. 2001;414:105–11.PubMedGoogle Scholar
  6. 6.
    Schatton T, Frank NY, Frank MH. Identification and targeting of cancer stem cells. Bioessays. 2009;10:1038–49.Google Scholar
  7. 7.
    Potter VR. Phenotypic diversity in experimental hepatomas: the concept of partially blocked ontogeny. The 10th Walter Hubert Lecture. Br J Cancer. 1978;38:1–23.PubMedGoogle Scholar
  8. 8.
    Rowan K. Are cancer stem cells real? After four decades, debate still simmers. JNCI. 2009;101:546–7.PubMedGoogle Scholar
  9. 9.
    Hadnagy A, Gaboury L, Beaulieu R. SP analysis may be used to identify cancer stem cell populations. Exp Cell Res. 2006;3123:701–10.Google Scholar
  10. 10.
    Piccirillo SG, Vescovi AL. Brain tumour stem cells: possibilities of new therapeutic strategies. Expert Opin Biol Ther. 2007;7:1129–35.PubMedGoogle Scholar
  11. 11.
    Dean M, Fojo T, Bates S. Tumor stem cells and drug resistance. Nat Rev Cancer. 2005;5:275–84.PubMedGoogle Scholar
  12. 12.
    Kimberly EF, Paola R, Clodia O, Lucio M. The cancer stem cell hypothesis. In: Bagley RG and Teicher BA (eds) Cancer drug discovery and development: stem cells and cancer. LLC:Humana Press Publishing, 2009, pp 3–14.Google Scholar
  13. 13.
    Zhou S, Morris JJ, Barnes Y, Lan L, Schuetz JD, Sorrentino BP. Bcrp1 gene expression is required for normal numbers of side population stem cells in mice, and confers relative protection to mitoxantrone in hematopoietic cells in vivo. Proc Natl Acad Sci USA. 2002;99:12339–44.PubMedGoogle Scholar
  14. 14.
    Lapidot T, Sirard C, Vormoor J, et al. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature. 1994;367:645–8.PubMedGoogle Scholar
  15. 15.
    Dou J, Pan M, Wen P, et al. Isolation and identification of cancer stem like cells from murine melanoma cell lines. Cell Mol Immunol. 2007;4:467–72.PubMedGoogle Scholar
  16. 16.
    Dou J, Wen P, Pan M, et al. Identification of tumor stem-like cells in mouse melanoma cell line by analysis characteristics of side population cells. Cell Bio Internat. 2009;33:807–15.Google Scholar
  17. 17.
    Alison MR, Islam S. Attributes of adult stem cells. J Pathol. 2009;217:144–60.PubMedGoogle Scholar
  18. 18.
    Dean M. Cancer stem cells and new therapeutic approaches. In: Sharmila B, editor. Cancer stem cells: identification and targets. New Jersey: John Wiley & Sons, Inc. Publishing; 2009. p. 217–32.Google Scholar
  19. 19.
    Wicha MS, Liu S, Dontu G. Cancer stem cells: an old idea—a paradigm shift. Cancer Res. 2006;66:1883–90.PubMedGoogle Scholar
  20. 20.
    Clarke MF, Dick JE, Dirks PB, et al. Cancer stem cells: perspectives on current status and future directions. AACR workshop on cancer stem cells. Cancer Res. 2006;66:9339–44.PubMedGoogle Scholar
  21. 21.
    Miraglia S, Godfrey W, Yin AH, et al. A novel five-transmembrane hematopoietic stem cell antigen: isolation, characterization, and molecular cloning. Blood. 1997;90:5013–21.PubMedGoogle Scholar
  22. 22.
    Kusumbe AP, Mali AM, Bapat SA. CD133-expressing stem cells associated with ovarian metastases establish an endothelial hierarchy and contribute to tumor vasculature. Stem Cells. 2009;27:498–508.PubMedGoogle Scholar
  23. 23.
    Suetsugu A, Nagaki M, Aoki H, Motohashi T, Kunisada T, Moriwaki H. Characterization of CD133+ hepatocellular carcinoma cells as cancer stem/progenitor cells. Biochem Biophys Res Commun. 2006;351:820–4.PubMedGoogle Scholar
  24. 24.
    Yao J, Zhang T, Ren J, Yu M, Wu G. Effect of CD133/prominin-1 antisense oligodeoxynucleotide on in vitro growth characteristics of Huh-7 human hepatocarcinoma cells and U251 human glioma cells. Oncol Rep. 2009;22:781–7.PubMedGoogle Scholar
  25. 25.
    Hermann PC, Huber SL, Herrler T, et al. Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell. 2007;1:313–23.PubMedGoogle Scholar
  26. 26.
    O’Brien CA, Pollett A, Gallinger S, Dick JE. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature. 2007;445:106–10.PubMedGoogle Scholar
  27. 27.
    Ricci-Vitiani L, Lombardi DG, Pilozzi E, et al. Identification and expansion of human colon-cancer-initiating cells. Nature. 2007;445:111–15.PubMedGoogle Scholar
  28. 28.
    Mizrak D, Brittan M, Alison MR. CD133: molecule of the moment. J Pathol. 2008;214:3–9.PubMedGoogle Scholar
  29. 29.
    Shmelkov JM, Butler AT, Hooper AH, et al. CD133 expression is not restricted to stem cells, and both CD133+ and CD133 metastatic colon cancer cells initiate tumors. J Clin Invest. 2008;118:2111–20.PubMedGoogle Scholar
  30. 30.
    Mark A, La B, Mina JB. Is CD133 a marker of metastatic colon cancer stem cells? J Clin Invest. 2008;118:2021–4.Google Scholar
  31. 31.
    Kasper S. Exploring the origins of the normal prostate and prostate cancer stem cell. Stem Cell Rev. 2008;4:193–201.PubMedGoogle Scholar
  32. 32.
    Cox CV, Diamanti P, Evely RS, et al. Expression of CD133 on leukemia initiating cells in childhood ALL. Blood. 2009;113:3287–96.PubMedGoogle Scholar
  33. 33.
    Kumamoto H, Ohki K. Detection of CD133, Bmi-1, and ABCG2 in ameloblastic tumors. J Oral Pathol Med 2009, [Epub ahead of print].Google Scholar
  34. 34.
    Zhu Z, Hao X, Yan M, et al. Cancer stem/progenitor cells are highly enriched in CD133(+)CD44(+) population in hepatocellular carcinoma. Int J Cancer 2009, [Epub ahead of print].Google Scholar
  35. 35.
    Curley MD, Therrien VA, Cummings CL, et al. CD133 expression defines a tumor initiating cell population in primary human ovarian cancer. Stem Cells. 2009;12:2875–83.Google Scholar
  36. 36.
    Yasuda H, Tanaka K, Saigusa S, et al. Elevated CD133, but not VEGF or EGFR, as a predictive marker of distant recurrence after preoperative chemoradiotherapy in rectal cancer. Oncol Rep. 2009;22:709–17.PubMedGoogle Scholar
  37. 37.
    Goodell MA, Brose K, Paradis G, Conner AS, Mulligan RC. Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J Exp Med. 1996;183:1797–806.PubMedGoogle Scholar
  38. 38.
    Zhou XD, Wang XY, Qu FJ. Detection of cancer stem cells from the C6 glioma cell line. J Int Med Res. 2009;37:503–10.PubMedGoogle Scholar
  39. 39.
    Hirschmann-Jax C, Foster AE, Wulf GG, et al. A distinct “side population” of cells with high drug efflux capacity in human tumor cells. Proc Natl Acad Sci USA. 2004;101:14228–33.PubMedGoogle Scholar
  40. 40.
    Grichnik JM, Burch JA, Schulteis RD, et al. Melanoma, a tumor based on a mutant stem cell? J Invest Dermatol. 2006;126:142–53.PubMedGoogle Scholar
  41. 41.
    Szotek PP, Pieretti-Vanmarcke R, Masiakos PT, et al. Ovarian cancer side population defines cells with stem cell–like characteristics and Mullerian inhibiting substance responsiveness. Proc Natl Acad Sci USA. 2006;103:11154–9.PubMedGoogle Scholar
  42. 42.
    Wang J, Guo LP, Chen LZ, et al. Identification of cancer stem cell-like side population cells in human nasopharyngeal carcinoma cell line. Cancer Res. 2007;67:3716–24.PubMedGoogle Scholar
  43. 43.
    Chiba T, Kita K, Zheng YW, et al. Side population purified from hepatocellular carcinoma cells harbors cancer stem cell-like properties. Hepatology. 2006;44:240–51.PubMedGoogle Scholar
  44. 44.
    Kondo T, Setoguchi T, Taga T. Persistence of a small subpopulation of cancer stem-like cells in the C6 glioma cell line. Proc Natl Acad Sci USA. 2004;101:781–6.PubMedGoogle Scholar
  45. 45.
    Dou J, Li Y, Hu W, et al. Identification of tumor stem like cells in mouse myeloma cell lines. Cell Mol Biol. 2009;55(Suppl):OL1151–60.PubMedGoogle Scholar
  46. 46.
    Collins AT, Berry PA, Hyde C, et al. Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res. 2005;65:10946–51.PubMedGoogle Scholar
  47. 47.
    Vega F, Davuluri Y, Cho-Vega, et al. Side population of a murine mantle cell lymphoma model contains tumor-initiating cells responsible for lymphoma maintenance and dissemination. J Cell Mol Med 2009, [Epub ahead of print].Google Scholar
  48. 48.
    Burkert J, Otto WR, Wright NA. Side populations of gastrointestinal cancers are not enriched in stem cells. J Pathol. 2008;214:564–73.PubMedGoogle Scholar
  49. 49.
    Xu JX, Morii E, Liu Y, Nakamichi N, Ikeda J, Kimura H, et al. High tolerance to apoptotic stimuli induced by serum depletion and ceramide in side-population cells: high expression of CD55 as a novel character for side-population. Exp Cell Res. 2007;313:1877–85.PubMedGoogle Scholar
  50. 50.
    Kondo T, Setoguchi T, Taga T. Persistence of a small subpopulation of cancer stemlike cells in the C6 glioma cell line. Proc Natl Acad Sci USA. 2004;101:781–6.PubMedGoogle Scholar
  51. 51.
    Grichnik JM, Burch JA, Schulteis RD, et al. Melanoma, a tumor based on a mutant stem cell? J Invest Dermatol. 2006;126:142–53.PubMedGoogle Scholar
  52. 52.
    Zhang X, Jiang CL, Wang BS, Liu Q, Zhao FS, Dou J. Primarily identification of the cell surface mark of ovarial cancer stem cells in a human ovarian cell line based on sorting side population cells. J Southeast University (Medical Science Edition). 2009;28:800–3.Google Scholar
  53. 53.
    Patrawala L, Calhoun T, Schneider-Broussard R, Zhou J, Claypool K, Tang DG. Side population is enriched in tumorigenic, stem-like cancer cells, whereas ABCG2+ and ABCG2-cancer cells are similarly tumorigenic. Cancer Res. 2005;65:6207–19.PubMedGoogle Scholar
  54. 54.
    Kim M, Turnquist H, Jackson J. The multidrug resistance transporter ABCG2 (Breast Cancer Resistance Protein 1) Effluxes Hoechst 33342 and is overexpressed in hematopoietic stem cells. Clin Cancer Res. 2002;8:22–8.PubMedGoogle Scholar
  55. 55.
    Henriksen U, Gether U, Litman T. Effect of Walker A mutation (K86M) on oligomerization and surface targeting of the multidrug resistance transporter ABCG2. J Cell Sci. 2005;118:1417–26.PubMedGoogle Scholar
  56. 56.
    An Y, Ongkeko WM. ABCG2: the key to chemoresistance in cancer stem cells? Expert Opin Drug Metab Toxicol. 2009;5:1529–42.PubMedGoogle Scholar
  57. 57.
    Frank NY, Margaryan A, Huang Y, et al. ABCB5-mediated doxorubicin transport and chemoresistance in human malignant melanoma. Cancer Res. 2005;65:4320–33.PubMedGoogle Scholar
  58. 58.
    Diah SK, Smitherman PK, Aldridge J, et al. Resistance to mitoxantrone in multidrug-resistant MCF-7 breast cancer cells evaluation og mitoxantrone transport and the role of multidrug resistance protein family proteins. Cancer Res. 2001;61:5461–7.PubMedGoogle Scholar
  59. 59.
    Christgen M, Ballmaier M, Bruchhardt H, von Wasielewski R, Kreipe H, Lehmann U. Identification of a distinct side population of cancer cells in the Cal-51 human breast carcinoma cell line. Mol Cell Biochem. 2007;306:201–12.PubMedGoogle Scholar
  60. 60.
    Graf GA, Li WP, Gerard RD. Coexpression of ATP-binding cassette proteins ABCG5 and ABCG8 permits their transport to the apical surface. J Clin Invest. 2002;110:659–69.PubMedGoogle Scholar
  61. 61.
    Gou S, Liu T, Wang C, et al. Establishment of clonal colony-forming assay for propagation of pancreatic cancer cells with stem cell properties. Pancreas. 2007;34:429–35.PubMedGoogle Scholar
  62. 62.
    Schatton T, Murphy GF, Frank NY, et al. Identification of cells initiating human melanomas. Nature. 2008;451:345–9.PubMedGoogle Scholar
  63. 63.
    Hamburger AW, Salmon SE. Primary bioassay of human tumor stem cells. Science. 1977;197:461–3.PubMedGoogle Scholar
  64. 64.
    Matsui W, Huff CA, Wang Q, et al. Characterization of clonogenic multiple myeloma cells. Blood. 2004;103:2332–6.PubMedGoogle Scholar
  65. 65.
    Gou S, Liu T, Wang C, Yin T, Li K, Yang M, et al. Establishment of clonal colony-forming assay for propagation of pancreatic cancer cells with stem cell properties. Pancreas. 2007;34:429–35.PubMedGoogle Scholar
  66. 66.
    Burkert J, Wright NA, Alison MR. Stem cells and cancer: an intimate relationship. J Pathol. 2006;209:287–97.PubMedGoogle Scholar
  67. 67.
    Chang CC, Sun W, Cruz A, Saitoh M, Tai MH, Trosko JE. A human breast epithelial cell type with stem cell characteristics as target cells for carcinogenesis. Radiat Res. 2001;155:201–7.PubMedGoogle Scholar
  68. 68.
    Quintana E, Shackleton M, Sabel MS, Fullen DR, Johnson TM, Morrison SJ. Efficient tumour formation by single human melanoma cells. Nature. 2008;456:593–8.PubMedGoogle Scholar
  69. 69.
    Gray-Schopfer V, Wellbrock C, Marais R. Melanoma biology and new targeted therapy. Nature. 2007;445:851–7.PubMedGoogle Scholar
  70. 70.
    Kerbel RS, Kamen BA. The anti-angiogenic basis of metronomic chemotherapy. Nat Rev Cancer. 2004;4:423–36.PubMedGoogle Scholar
  71. 71.
    Ischenko I, Seeliger H, Schaffer M, Jauch KW, Bruns CJ. Cancer stem cells: how can we target them? Curr Med Chem. 2008;15:3171–84.PubMedGoogle Scholar
  72. 72.
    Brabletz T, Jung A, Spaderna S, Hlubek F, Kirchner T. Migrating cancer stem cells—an integrated concept of malignant tumour progression. Nat Rev Cancer. 2005;5:744–9.PubMedGoogle Scholar
  73. 73.
    Leah O, Benjamin T, Yibin K. Cancer stem cells and metastasis: emerging themes and therapeutic implications. In: Bagley RG and Teicher BA, (eds) Cancer drug discovery and development: stem cells and cancer. LLC: Humana Press Publishing; 2009, pp 92–109.Google Scholar
  74. 74.
    Leonard Z. Foreword. In: John S Yu, (eds) Cancer stem cells. Humana Press. Heidelberg London New York Publishing, 2009, pp 1–5.Google Scholar
  75. 75.
    Eriksson M, Guse K, Bauerschmitz G, Virkkunen P, et al. Oncolytic adenoviruses kill breast cancer initiating CD44+CD24−/low cells. Mol Ther. 2007;15:2088–93.PubMedGoogle Scholar
  76. 76.
    Jiang H, Gomez-Manzano C, Aoki H, et al. Examination of the therapeutic potential of Delta-24-RGD in brain tumor stem cells: role of autophagic cell death. J Natl Cancer Inst. 2007;99:1410–14.PubMedGoogle Scholar
  77. 77.
    Ischenko I, Seeliger H, Schaffer M, Jauch KW, Christiane JB. Cancer stem cells: how can we target them? Curr Med Chem. 2008;15:3171–84.PubMedGoogle Scholar
  78. 78.
    Preacok CD, Wang Q, Gesell GS, et al. Hedgehog signaling maintains a tumor stem cell compartment in multiple myeloma. Proc Natl Acad Sci USA. 2007;104:4048–53.Google Scholar
  79. 79.
    Woodward WA, Chen MS, Behbod F, Alfaro MP, Buchholz TA, Rosen JM. WNT/β-catenin mediates radiation resistance of mouse mammary progenitor cells. Proc Natl Acad Sci USA. 2007;104:618–23.PubMedGoogle Scholar
  80. 80.
    Pu P, Zhang Z, Kang C, et al. Downregulation of Wnt2 and beta-catenin by siRNA suppresses malignant glioma cell growth. Cancer Gene Ther. 2009;16:351–61.PubMedGoogle Scholar
  81. 81.
    Malanchi I, Peinado H, Kassen D, et al. Cutaneous cancer stem cell maintenance is dependent on beta-catenin signalling. Nuture. 2008;452:650–3.Google Scholar
  82. 82.
    Rappa G, Fodstad O, Lorico A. The stem cell-associated antigen CD133 (Prominin-1) is a molecular therapeutic target for metastatic melanoma. Stem Cells. 2008;26:3008–17.PubMedGoogle Scholar
  83. 83.
    Schatton T, Murphy GF, Frank NY, et al. Identification of cells initiating human melanomas. Nature. 2008;451:345–9.PubMedGoogle Scholar
  84. 84.
    Cuilian J, Dou J. Primarily identification of ovarial cancer stem cells in a human ovarian cell line based on sorting side population cells. A Dissertation of the Academic Degree in Southeast University, China.2009, pp 26–30.Google Scholar
  85. 85.
    Presta LG, Chen H, O’Connor SJ, et al. Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. Cancer Res. 1997;57:4593–9.PubMedGoogle Scholar
  86. 86.
    Hurwitz J, Fehrenbacher L, Novonty W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. New Eng J Med. 2004;350:2335–42.PubMedGoogle Scholar
  87. 87.
    Hiratsuka S, Watanabe A, Aburatani H, Maru Y. Tumour-mediated upregulation of chemoattractants and recruitment of myeloid cells predetermines lung metastasis. Nat Cell Biol. 2006;8:1369–75.PubMedGoogle Scholar
  88. 88.
    Sanjay KS, Mohamedi NK, Sadhan M. MicroRNAs in Stem Cells and Cancer Stem Cells. In: John S Yu (eds) Cancer stem cells. Humana Press. Heidelberg London New York Publishing, 2009, 62–80.Google Scholar
  89. 89.
    Shimono Y, Zabala M, Cho RW, et al. Downregulation of miRNA-200c links breast cancer stem cells with normal stem cells. Cell. 2009;138:592–603.PubMedGoogle Scholar
  90. 90.
    Ryan MO, Dinesh SR, Aadel AC, David B. Physiological and pathological roles for microRNAs in the immune system. Nat Rev Immnuol. 2010;10:111–22.Google Scholar
  91. 91.
    Dirks PB. MicroRNAs and parallel stem cell lives. Cell. 2009;138:423–4.PubMedGoogle Scholar
  92. 92.
    Xu N, Papagiannakopoulos T, Pan G, Thomson JA, Kosik KS. MicroRNA-145 regulates OCT4, SOX2, and KLF4 and represses pluripotency in human embryonic stem cells. Cell. 2009;137:647–58.PubMedGoogle Scholar
  93. 93.
    Ulrike B, Jorg S, Ulrich W, et al. A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells. EMBO Rep. 2008;9:582–9.Google Scholar
  94. 94.
    Ulrich W, Jörg S, Ulrike C, et al. The EMT-activator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microRNAs. Nat Cell Biol. 2009;12:1487–95.Google Scholar
  95. 95.
    Ji Q, Hao X, Zhang M, et al. MicroRNA miR-34 inhibits human pancreatic cancer tumor-initiating cells. PLoS ONE. 2009;4:e6816–24.PubMedGoogle Scholar
  96. 96.
    Griffith LG, Swartz MA. Capturing complex 3D tissue physiology in vitro. Nat Rev Mol Cell Biol. 2006;7:211–24.PubMedGoogle Scholar
  97. 97.
    Yamada KM, Cukierman E. Modeling tissue morphogenesis and cancer in 3D. Cell. 2007;130:601–10.PubMedGoogle Scholar
  98. 98.
    Nelson CM, Bissell MJ. Of extracellular matrix, scaffolds, and signaling: tissue architecture regulates development, homeostasis, and cancer. Annu Rev Cell Dev Biol. 2006;22:287–309.PubMedGoogle Scholar
  99. 99.
    Knight ZA, Shokat KM. Chemical genetics: where genetics and pharmacology meet. Cell. 2007;128:425–30.PubMedGoogle Scholar
  100. 100.
    Hebner C, Weaver VM, Debnath J. Modeling morphogenesis and oncogenesis in three-dimensional breast epithelial cultures. Annu Rev Pathol. 2008;3:313–39.PubMedGoogle Scholar
  101. 101.
    Tomei AA, Boschetti F, Gervaso F, Swartz MA. 3D collagen cultures under well-defined dynamic strain: a novel strain device with a porous elastomeric support. Biotechnol Bioeng. 2009;103:217–25.PubMedGoogle Scholar
  102. 102.
    Kenny PA, Lee GY, Myers CA, Neve RM, Semeiks JR, Bissell MJ. The morphologies of breast cancer cell lines in three-dimensional assays correlate with their profiles of gene expression. Mol Oncol. 2007;1:84–96.PubMedGoogle Scholar
  103. 103.
    Castelló-Cros R, Khan DR, Simons J, Valianou M, Cukierman E. Staged stromal extracellular 3D matrices differentially regulate breast cancer cell responses through PI3K and beta1-integrins. BMC Cancer. 2009;9:94.PubMedGoogle Scholar
  104. 104.
    Quiros RM, Valianou M, Kwon Y, Brown KM, Godwin AK, Cukierman E. Ovarian normal and tumor-associated fibroblasts retain in vivo stromal characteristics in a 3-D matrix-dependent manner. Gynecol Oncol. 2008;110:99–109.PubMedGoogle Scholar
  105. 105.
    Serena P, Gaetano F. Dendritic cell vaccines for cancer stem cells. Stem cells and cancer. In: John S Yu (eds). Cancer stem cells. Humana Press. Heidelberg London New York Publishing; 2009, pp 233–47.Google Scholar
  106. 106.
    Tobias S, Markus HF. Antitumor immunity and cancer stem cells. Ann NY Acad Sci. 2009;1176:154–69.Google Scholar
  107. 107.
    Tobias S, Markus HF. Cancer stem cells and human malignant melanoma. Pigment Cell Melanoma Res. 2008;21:39–55.Google Scholar
  108. 108.
    Mapara MY, Sykes M. Tolerance and cancer: mechanisms of tumor evasion and strategies for breaking tolerance. J Clin Oncol. 2004;22:1136–51.PubMedGoogle Scholar
  109. 109.
    Pietra G, Manzini C, Vitale M, et al. Natural killer cells kill human melanoma cells with characteristics of cancer stem cells. Inter Immunol. 2009;21:793–801.Google Scholar
  110. 110.
    Yamanaka R, Homma J, Yajima N, et al. Clinical evaluation of dendritic cell vaccination for patients with recurrent glioma: results of a clinical phase I/II trial. Clin Cancer Res. 2005;11:4160–7.PubMedGoogle Scholar
  111. 111.
    Xu QJ, Liu GT, Yuan XP, et al. Antigen-specific T-cell response from dendritic cell vaccination using cancer stem-like cell-associated antigens. Stem Cells. 2009;27:1734–40.PubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2010

Authors and Affiliations

  1. 1.Department of Pathogenic Biology and Immunology, School of Basic Medical ScienceSoutheast UniversityNanjingChina
  2. 2.School of Biological Science & Medical EngineeringSoutheast UniversityNanjingChina

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