Seminars in Radiation Oncology
Volume 19, Issue 2 , Pages 78-86 , April 2009

Therapeutic Implications of the Cancer Stem Cell Hypothesis

  • Maximilian Diehn, MD, PhD

      Affiliations

    • Department of Radiation Oncology, Stanford University, School of Medicine, Stanford, CA
    • Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford Cancer Center and Ludwig Center at Stanford, Stanford University, School of Medicine, Stanford, CA
    • ,
  • Robert W. Cho, MD

      Affiliations

    • Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford Cancer Center and Ludwig Center at Stanford, Stanford University, School of Medicine, Stanford, CA
    • Department of Pediatrics, Division of Stem Cell Transplantation, Stanford University, School of Medicine, Stanford, CA
    • ,
  • Michael F. Clarke, MD

      Affiliations

    • Department of Pediatrics, Division of Stem Cell Transplantation, Stanford University, School of Medicine, Stanford, CA
    • Department of Medicine, Stanford University, School of Medicine, Stanford, CA
    • Corresponding Author InformationAddress reprint requests to Michael F. Clarke, MD, Stanford Institutes of Medicine, 1050 Arastradero Road (Lower Bldg), Room A151, MC: 5542, Palo Alto, CA 94304

References 

  1. Deome KB, Faulkin LJ, Bern HA, et al. Development of mammary tumors from hyperplastic alveolar nodules transplanted into gland-free mammary fat pads of female C3H mice. Cancer Res. 1959;19:515–520
  2. Kordon EC, Smith GH. An entire functional mammary gland may comprise the progeny from a single cell. Development. 1998;125:1921–1930
  3. Tsai YC, Lu Y, Nichols PW, et al. Contiguous patches of normal human mammary epithelium derived from a single stem cell: Implications for breast carcinogenesis. Cancer Res. 1996;56:402–404
  4. Shackleton M, Vaillant F, Simpson KJ, et al. Generation of a functional mammary gland from a single stem cell. Nature. 2006;439:84–88
  5. Stingl J, Eirew P, Ricketson I, et al. Purification and unique properties of mammary epithelial stem cells. Nature. 2006;439:993–997
  6. Bruce WR, Van Der Gaag H. A quantitative assay for the number of murine lymphoma cells capable of proliferation in Vivo. Nature. 1963;199:79–80
  7. Hewitt HB, Blake ER, Walder AS. A critique of the evidence for active host defence against cancer, based on personal studies of 27 murine tumours of spontaneous origin. Br J Cancer. 1976;33:241–259
  8. Hill RP, Milas L. The proportion of stem cells in murine tumors. Int J Radiat Oncol Biol Phys. 1989;16:513–518
  9. Hamburger AW, Salmon SE. Primary bioassay of human tumor stem cells. Science. 1977;197:461–463
  10. West CM, Davidson SE, Hunter RD. Evaluation of surviving fraction at 2 Gy as a potential prognostic factor for the radiotherapy of carcinoma of the cervix. Int J Radiat Biol. 1989;56:761–765
  11. Bonnet D, Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med. 1997;3:730–737
  12. Lapidot T, Sirard C, Vormoor J, et al. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature. 1994;367:645–648
  13. Al-Hajj M, Wicha MS, Benito-Hernandez A, et al. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A. 2003;100:3983–3988
  14. Singh SK, Hawkins C, Clarke ID, et al. Identification of human brain tumour initiating cells. Nature. 2004;432:396–401
  15. Collins AT, Berry PA, Hyde C, et al. Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res. 2005;65:10946–10951
  16. Dalerba P, Dylla SJ, Park IK, et al. Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci U S A. 2007;104:10158–10163
  17. O'Brien CA, Pollett A, et al. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature. 2007;445:106–110
  18. Prince ME, Sivanandan R, Kaczorowski A, et al. Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proc Natl Acad Sci U S A. 2007;104:973–978
  19. Li C, Heidt DG, Dalerba P, et al. Identification of pancreatic cancer stem cells. Cancer Res. 2007;67:1030–1037
  20. 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 Cells. 2007;1:313–323
  21. Yang ZF, Ho DW, Ng MN, et al. Significance of CD90+ cancer stem cells in human liver cancer. Cancer Cells. 2008;13:153–166
  22. Reya T, Morrison SJ, Clarke MF, et al. Stem cells, cancer, and cancer stem cells. Nature. 2001;414:105–111
  23. Dangles-Marie V, Pocard M, Richon S, et al. Establishment of human colon cancer cell lines from fresh tumors versus xenografts: Comparison of success rate and cell line features. Cancer Res. 2007;67:398–407
  24. Ho MM, Ng AV, Lam S, et al. Side population in human lung cancer cell lines and tumors is enriched with stem-like cancer cells. Cancer Res. 2007;67:4827–4833
  25. Patrawala L, Calhoun T, Schneider-Broussard R, et al. Side population is enriched in tumorigenic, stem-like cancer cells, whereas ABCG2+ and ABCG2-cancer cells are similarly tumorigenic. Cancer Res. 2005;65:6207–6219
  26. Todaro M, Alea MP, Di Stefano AB, et al. Colon cancer stem cells dictate tumor growth and resist cell death by production of interleukin-4 (Cell). Stem Cells. 2007;1:389–402
  27. Dylla SJ, Beviglia L, Park IK, et al. Colorectal cancer stem cells are enriched in xenogeneic tumors following chemotherapy. PLoS ONE. 2008;3:e2428
  28. Li X, Lewis MT, Huang J, et al. Intrinsic resistance of tumorigenic breast cancer cells to chemotherapy. J Natl Cancer Inst. 2008;100:672–679
  29. Ishikawa F, Yoshida S, Saito Y, et al. Chemotherapy-resistant human AML stem cells home to and engraft within the bone-marrow endosteal region. Nat Biotechnol. 2007;25:1315–1321
  30. Kobielak K, Stokes N, de la Cruz J, et al. Loss of a quiescent niche but not follicle stem cells in the absence of bone morphogenetic protein signaling. Proc Natl Acad Sci U S A. 2007;104:10063–10068
  31. Barker N, van Es JH, Kuipers J, et al. Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature. 2007;449:1003–1007
  32. 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 U S A. 2004;101:14228–14233
  33. Dean M, Fojo T, Bates S. Tumour stem cells and drug resistance. Nat Rev Cancer. 2005;5:275–284
  34. Donnenberg VS, Donnenberg AD. Multiple drug resistance in cancer revisited: The cancer stem cell hypothesis. J Clin Pharmacol. 2005;45:872–877
  35. Ginestier C, Hur MH, Charafe-Jauffret E, et al. ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome (Cell). Stem Cells. 2007;1:555–567
  36. Easterday MC, Dougherty JD, Jackson RL, et al. Neural progenitor genes (Germinal zone expression and analysis of genetic overlap in stem cell populations). Dev Biol. 2003;264:309–322
  37. Forsberg EC, Prohaska SS, Katzman S, et al. Differential expression of novel potential regulators in hematopoietic stem cells. PLoS Genet. 2005;1:e28
  38. Park IK, He Y, Lin F, et al. Differential gene expression profiling of adult murine hematopoietic stem cells. Blood. 2002;99:488–498
  39. Park IK, Qian D, Kiel M, et al. Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells. Nature. 2003;423:302–305
  40. Park I-K, Klug CA, Li K, et al. Molecular cloning and characterization of a novel regulator of G protein signaling from mouse hematopoietic stem cells. J Biol Chem. 2001;276:915–923
  41. Ponta H, Sherman L, Herrlich PA. CD44: from adhesion molecules to signalling regulators. Nat Rev Mol Cell Biol. 2003;4:33–45
  42. Jin L, Hope KJ, Zhai Q, et al. Targeting of CD44 eradicates human acute myeloid leukemic stem cells. Nat Med. 2006;12:1167–1174
  43. Marhaba R, Zoller M. CD44 in cancer progression: Adhesion, migration and growth regulation. J Mol Histol. 2004;35:211–231
  44. Cameron DA, Stein S. Drug insight: Intracellular inhibitors of HER2—Clinical development of lapatinib in breast cancer. Nat Clin Pract Oncol. 2008;5:512–520
  45. Dinh P, de Azambuja E, Cardoso F, et al. Facts and controversies in the use of trastuzumab in the adjuvant setting. Nat Clin Pract Oncol. 2008;
  46. Korkaya H, Paulson A, Iovino F, et al. HER2 regulates the mammary stem/progenitor cell population driving tumorigenesis and invasion. Oncogene. 2008;27:6120–6130
  47. Cho R, Wang X, Diehn M, et al. Isolation and molecular characterization of cancer stem cells in MMTV-Wnt-1 murine breast tumors. Stem Cells. 2008;26:364–371
  48. Dontu G, Jackson KW, McNicholas E, et al. Role of Notch signaling in cell-fate determination of human mammary stem/progenitor cells. Breast Cancer Res. 2004;6:R605–R615
  49. Liu S, Dontu G, Mantle ID, et al. Hedgehog signaling and Bmi-1 regulate self-renewal of normal and malignant human mammary stem cells. Cancer Res. 2006;66:6063–6071
  50. Dovey JS, Zacharek SJ, Kim CF, et al. Bmi1 is critical for lung tumorigenesis and bronchioalveolar stem cell expansion. Proc Natl Acad Sci U S A. 2008;105:11857–11862
  51. Leung C, Lingbeek M, Shakhova O, et al. Bmi1 is essential for cerebellar development and is overexpressed in human medulloblastomas. Nature. 2004;428:337–341
  52. Yilmaz OH, Valdez R, Theisen BK, et al. PTEN dependence distinguishes haematopoietic stem cells from leukaemia-initiating cells. Nature. 2006;441:475–482
  53. Lee J, Son MJ, Woolard K, et al. Epigenetic-mediated dysfunction of the bone morphogenetic protein pathway inhibits differentiation of glioblastoma-initiating cells. Cancer Cells. 2008;13:69–80
  54. Piccirillo SG, Reynolds BA, Zanetti N, et al. Bone morphogenetic proteins inhibit the tumorigenic potential of human brain tumour-initiating cells. Nature. 2006;444:761–765
  55. Guzman ML, Rossi RM, Karnischky L, et al. The sesquiterpene lactone parthenolide induces apoptosis of human acute myelogenous leukemia stem and progenitor cells. Blood. 2005;105:4163–4169
  56. Liu R, Wang X, Chen GY, et al. The prognostic role of a gene signature from tumorigenic breast-cancer cells. N Engl J Med. 2007;356:217–226
  57. Fialkow PJ. Use of genetic markers to study cellular origin and development of tumors in human females. Adv Cancer Res. 1972;15:191–226
  58. Fialkow PJ. Stem cell origin of human myeloid blood cell neoplasms. Verh Dtsch Ges Pathol. 1990;74:43–47
  59. Fialkow PJ, Singer JW, Adamson JW, et al. Acute nonlymphocytic leukemia: Heterogeneity of stem cell origin. Blood. 1981;57:1068–1073
  60. Jamieson CH, Ailles LE, Dylla SJ, et al. Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis CML. N Engl J Med. 2004;351:657–667
  61. Krivtsov AV, Twomey DZ, Feng Z, et al. Transformation from committed progenitor to leukaemia stem cell initiated by MLL-Af 9. Nature. 2006;442:818–822
  62. Odoux C, Fohrer H, Hoppo T, et al. A stochastic model for cancer stem cell origin in metastatic colon cancer. Cancer Res. 2008;68:6932–6941
  63. Abratt RP, Brune D, Dimopoulos MA, et al. Randomised phase III study of intravenous vinorelbine plus hormone therapy versus hormone therapy alone in hormone-refractory prostate cancer. Ann Oncol. 2004;15:1613–1621
  64. Huff CA, Matsui W, Smith BD, et al. The paradox of response and survival in cancer therapeutics. Blood. 2006;107:431–434
  65. Rocha Lima CM, Green MR, Rotche R, et al. Irinotecan plus gemcitabine results in no survival advantage compared with gemcitabine monotherapy in patients with locally advanced or metastatic pancreatic cancer despite increased tumor response rate. J Clin Oncol. 2004;22:3776–3783
  66. Balic M, Lin H, Young L, et al. Most early disseminated cancer cells detected in bone marrow of breast cancer patients have a putative breast cancer stem cell phenotype. Clin Cancer Res. 2006;12:5615–5621
  67. Honeth G, Bendahl PO, Ringner M, et al. The CD44+/CD24− phenotype is enriched in basal-like breast tumors. Breast Cancer Res. 2008;10:R53
  68. Horwitz KB, Dye WW, Harrell JC, et al. Rare steroid receptor-negative basal-like tumorigenic cells in luminal subtype human breast cancer xenografts. Proc Natl Acad Sci U S A. 2008;105:5774–5779
  69. Hart LS, El-Deiry WS. Invincible, but not invisible: Imaging approaches toward in-vivo detection of cancer stem cells. J Clin Oncol. 2008;26:2901–2910

 MFC is a member of the paid advisory board of Oncomed Pharmaceuticals, Inc, and owns stock options in the company.

PII: S1053-4296(08)00078-7

doi: 10.1016/j.semradonc.2008.11.002

Seminars in Radiation Oncology
Volume 19, Issue 2 , Pages 78-86 , April 2009

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