Cancer Letters
Volume 286, Issue 2 , Pages 145-153 , 28 December 2009

Cancer stem cells in hepatocellular carcinoma: Recent progress and perspective

  • Tetsuhiro Chiba

      Affiliations

    • Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan
    • JST, CREST, Sanbancho, Chiyoda-ku, Tokyo 102-0075, Japan
  • ,
  • Akihide Kamiya

      Affiliations

    • Division of Stem Cell Therapy, Center for Stem Cell and Regenerative Medicine, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan
  • ,
  • Osamu Yokosuka

      Affiliations

    • Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan
  • ,
  • Atsushi Iwama

      Affiliations

    • Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan
    • JST, CREST, Sanbancho, Chiyoda-ku, Tokyo 102-0075, Japan
    • Corresponding Author InformationCorresponding author. Address: Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan. Tel.: +81 43 2262189; fax: +81 43 2262191.

Received 3 March 2009 ,Revised 23 April 2009 ,Accepted 23 April 2009.

References 

  1. Fialkow PJ, Gartler SM, Yoshida A. Clonal origin of chronic myelocytic leukemia in man. Proc. Natl. Acad. Sci. USA. 1967;58:1468–1471
  2. Fialkow PJ. Use of genetic markers to study cellular origin and development of tumors in human females. Adv. Cancer Res. 1972;15:191–226
  3. Heppner GH. Tumor heterogeneity. Cancer Res. 1984;44:2259–2265
  4. Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature. 2001;414:105–111
  5. Shafritz DA, Oertel M, Menthena A, Nierhoff D, Dabeva MD. Liver stem cells and prospects for liver reconstitution by transplanted cells. Hepatology. 2006;43:S89–98
  6. 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;100:3983–3988
  7. O’Brien CA, Pollett A, Gallinger S, Dick JE. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature. 2007;445:106–110
  8. Jamieson CH, Weissman IL, Passegué E. Chronic versus acute myelogenous leukemia: a question of self-renewal. Cancer Cell. 2004;6:531–533
  9. Wang JC, Dick JE. Cancer stem cells: lessons from leukemia. Trends Cell Biol. 2005;15:494–501
  10. Jordan CT, Guzman ML, Noble M. Cancer stem cells. New Engl. J. Med. 2006;355:1253–1261
  11. Befeler AS, Di Bisceglie AM. Hepatocellular carcinoma: diagnosis and treatment. Gastroenterology. 2002;122:1609–1619
  12. Lau WY, Lai EC. Hepatocellular carcinoma: current management and recent advances. Hepatob. Pancreat. Dis. Int. 2008;7:237–257
  13. Michalopoulos GK, DeFrances MC. Liver regeneration. Science. 1997;276:60–66
  14. Sell S. Heterogeneity and plasticity of hepatocyte lineage cells. Hepatology. 2001;33:738–750
  15. Walkup MH, Gerber DA. Hepatic stem cells: in search of Stem cells. 2006;24:1833–1840
  16. Mishra L, Banker T, Murray J, Byers S, Thenappan A, He AR, et al. Liver stem cells and hepatocellular carcinoma. Hepatology. 2009;49:318–329
  17. Zaret KS, Grompe M. Generation and regeneration of cells of the liver and pancreas. Science. 2008;322:1490–1494
  18. Kubota H, Reid LM. Clonogenic hepatoblasts, common precursors for hepatocytic and biliary lineages, are lacking classical major histocompatibility complex class I antigen. Proc. Natl. Acad. Sci. USA. 2000;97:12132–12137
  19. Watanabe T, Nakagawa K, Ohata S, Kitagawa D, Nishitai G, Seo J, et al. SEK1/MKK4-mediated SAPK/JNK signaling participates in embryonic hepatoblast proliferation via a pathway different from NF-κB-induced anti-apoptosis. Dev. Biol. 2002;250:332–347
  20. Nitou M, Sugiyama Y, Ishikawa K, Shiojiri N. Purification of fetal mouse hepatoblasts by magnetic beads coated with monoclonal anti-e-cadherin antibodies and their in vitro culture. Exp. Cell Res. 2002;279:330–343
  21. Tanimizu N, Nishikawa M, Saito H, Tsujimura T, Miyajima A. Isolation of hepatoblasts based on the expression of Dlk/Pref-1. J. Cell Sci. 2003;116:1775–1786
  22. Oertel M, Menthena A, Chen YQ, Teisner B, Jensen CH, Shafritz DA. Purification of fetal liver stem/progenitor cells containing all the repopulation potential for normal adult rat liver. Gastroenterology. 2008;134:823–832
  23. Suzuki A, Zheng YW, Kaneko S, Onodera M, Fukao K, Nakauchi H, et al. Clonal identification and characterization of self-renewing pluripotent stem cells in the developing liver. J. Cell Biol. 2002;156:173–184
  24. Suzuki A, Iwama A, Miyashita H, Nakauchi H, Taniguchi H. Role for growth factors and extracellular matrix in controlling differentiation of prospectively isolated hepatic stem cells. Development. 2003;130:2513–2524
  25. Schmelzer E, Zhang L, Bruce A, Wauthier E, Ludlow J, Yao HL, et al. Human hepatic stem cells from fetal and postnatal donors. J. Exp. Med. 2007;204:1973–1987
  26. Farber E. Similarities in the sequence of early histological changes induced in the liver of the rat by ethionine, 2-acetylamino-fluorene, and 3′-methyl-4-dimethylaminoazobenzene. Cancer Res. 1956;16:142–149
  27. Rountree CB, Barsky L, Ge S, Zhu J, Senadheera S, Crooks GM. A CD133-expressing murine liver oval cell population with bilineage potential. Stem Cells. 2007;25:2419–2429
  28. Petersen BE, Goff JP, Greenberger JS, Michalopoulos GK. Hepatic oval cells express the hematopoietic stem cell marker Thy-1 in the rat. Hepatology. 1998;27:433–445
  29. Petersen BE, Grossbard B, Hatch H, Pi L, Deng J, Scott EW. Mouse A6-positive hepatic oval cells also express several hematopoietic stem cell markers. Hepatology. 2003;37:632–640
  30. Menthena A, Deb N, Oertel M, Grozdanov PN, Sandhu J, Shah S, et al. Bone marrow progenitors are not the source of expanding oval cells in injured liver. Stem Cells. 2004;22:1049–1061
  31. Wang X, Foster M, Al-Dhalimy M, Lagasse E, Finegold M, Grompe M. The origin and liver repopulating capacity of murine oval cells. Proc. Natl. Acad. Sci. USA. 2003;100:11881–11888
  32. Yovchev MI, Grozdanov PN, Zhou H, Racherla H, Guha C, Dabeva MD. Identification of adult hepatic progenitor cells capable of repopulating injured rat Liver. Hepatology. 2008;47:636–647
  33. Kuwahara R, Kofman AV, Landis CS, Swenson ES, Barendswaard E, Theise ND, et al. The hepatic stem cell niche: identification by label-retaining cell assay. Hepatology. 2008;47:1994–2002
  34. Al-Hajj M, Clarke MF. Self-renewal and solid tumor stem cells. Oncogene. 2004;23:7274–7282
  35. Wu C, A Alman B. Side population cells in human cancers. Cancer Lett. 2008;268:1–9
  36. Hirschmann-Jax C, Foster AE, Wulf GG, Nuchtern JG, Jax TW, Gobel U, et al. A distinct “side population” of cells with high drug efflux capacity in human tumor cells. Proc. Natl. Acad. Sci. USA. 2004;101:14228–14233
  37. Chiba T, Kita K, Zheng YW, Yokosuka O, Saisho H, Iwama A, et al. Side population purified from hepatocellular carcinoma cells harbors cancer stem cell-like properties. Hepatology. 2006;44:240–251
  38. 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;101:781–786
  39. Zheng X, Shen G, Yang X, Liu W. Most C6 cells are cancer stem cells: evidence from clonal and population analyses. Cancer Res. 2007;67:3691–3697
  40. Platet N, Mayol JF, Berger F, Hérodin F, Wion D. Fluctuation of the SP/non-SP phenotype in the C6 glioma cell line. FEBS Lett. 2007;581:1435–1440
  41. Lichtenauer UD, Shapiro I, Geiger K, Quinkler M, Fassnacht M, Nitschke R, et al. Side population does not define stem cell-like cancer cells in the adrenocortical carcinoma cell line NCI h295R. Endocrinology. 2008;149:1314–1322
  42. Yin S, Li J, Hu C, Chen X, Yao M, Yan M, et al. CD133 positive hepatocellular carcinoma cells possess high capacity for tumorigenicity. Int. J. Cancer. 2007;120:1444–1450
  43. Ma S, Chan KW, Hu L, Lee TK, Wo JY, Ng IO, et al. Identification and characterization of tumorigenic liver cancer stem/progenitor cells. Gastroenterology. 2007;132:2542–2556
  44. Rountree CB, Senadheera S, Mato JM, Crooks GM, Lu SC. Expansion of liver cancer stem cells during aging in methionine adenosyltransferase 1A-deficient mice. Hepatology. 2008;47:1288–1297
  45. Rountree CB, Ding W, He L, Stiles B. Expansion of CD133 expressing liver cancer stem cells in liver specific PTEN deleted mice. Stem Cells. 2009;27:290–299
  46. Yang W, Yan HX, Chen L, Liu Q, He YQ, Yu LX, et al. Wnt/beta-catenin signaling contributes to activation of normal and tumorigenic liver progenitor cells. Cancer Res. 2008;68:4287–4295
  47. Yamashita T, Ji J, Budhu A, Forgues M, Yang W, Wang HY, et al. EpCAM-positive hepatocellular carcinoma cells are tumor-initiating cells with stem/progenitor cell features. Gastroenterology. 2009;136:1012–1024
  48. Yang ZF, Ho DW, Ng MN, Lau CK, Yu WC, Ngai P, et al. Significance of CD90+ cancer stem cells in human liver cancer. Cancer Cell. 2008;13:153–166
  49. Quintana E, Shackleton M, Sabel MS, Fullen DR, Johnson TM, Morrison SJ, et al. Efficient tumour formation by single human melanoma cells. Nature. 2008;456:593–598
  50. Potter VR, The 10th Walter Hubert Lecture Phenotypic diversity in experimental hepatomas: the concept of partially blocked ontogeny. Br. J. Cancer. 1978;38:1–23
  51. Dumble ML, Croager EJ, Yeoh GC, Quail EA. Generation and characterization of p53 null transformed hepatic progenitor cells: oval cells give rise to hepatocellular carcinoma. Carcinogenesis. 2002;23:435–445
  52. Steinberg P, Steinbrecher R, Radaeva S, Schirmacher P, Dienes HP, Oesch F, et al. Oval cell lines OC/CDE 6 and OC/CDE 22 give rise to cholangio-cellular and undifferentiated carcinomas after transformation. Lab. Invest. 1994;71:700–709
  53. Lowes KN, Brennan BA, Yeoh GC, Olynyk JK. Oval cell numbers in human chronic liver diseases are directly related to disease severity. Am. J. Pathol. 1999;154:537–541
  54. Roskams T. Liver stem cells and their implication in hepatocellular and cholangiocarcinoma. Oncogene. 2006;25:3818–3822
  55. Theise ND, Yao JL, Harada K, Hytiroglou P, Portmann B, Thung SN, et al. Hepatic ‘stem cell’ malignancies in adults: four cases. Histopathology. 2003;43:263–271
  56. Chiba T, Zheng YW, Kita K, Yokosuka O, Saisho H, Onodera M, et al. Enhanced selfrenewal capability in hepatic stem/progenitor cells drives cancer initiation. Gastroenterology. 2007;133:937–950
  57. Suzuki A, Sekiya S, Onishi M, Oshima N, Kiyonari H, Nakauchi H, et al. Flow cytometric isolation and clonal identification of self-renewing bipotent hepatic progenitor cells in adult mouse liver. Hepatology. 2008;48:1964–1978
  58. Lee JS, Heo J, Libbrecht L, Chu IS, Kaposi-Novak P, Calvisi DF, et al. A novel prognostic subtype of human hepatocellular carcinoma derived from hepatic progenitor cells. Nat. Med. 2006;12:410–416
  59. Yamashita T, Forgues M, Wang W, Kim JW, Ye Q, Jia H, et al. EpCAM and alpha-fetoprotein expression defines novel prognostic subtypes of hepatocellular carcinoma. Cancer Res. 2008;68:1451–1461
  60. Pardal R, Clarke MF, Morrison SJ. Applying the principles of stem-cell biology to cancer. Nat. Rev. Cancer. 2003;3:895–902
  61. Hill R, Wu H. PTEN, stem cells, and cancer stem cells. J. Biol. Chem. 2009;284:11755–11759
  62. Yilmaz OH, Valdez R, Theisen BK, Guo W, Ferguson DO, Wu H, et al. Pten dependence distinguishes haematopoietic stem cells from leukaemia-initiating cells. Nature. 2006;441:475–482
  63. Valk-Lingbeek ME, Bruggeman SW, van Lohuizen M. Stem cells and cancer; the polycomb connection. Cell. 2004;118:409–418
  64. Park IK, Morrison SJ, Clarke MF. Bmi1, stem cells, and senescence regulation. J. Clin. Invest. 2004;113:175–179
  65. Sparmann A, van Lohuizen M, fate Polycomb silencers control cell. development and cancer. Nat. Rev. Cancer. 2006;6:846–856
  66. Prince ME, Sivanandan R, Kaczorowski A, Wolf GT, Kaplan MJ, Dalerba P, et al. Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proc. Natl. Acad. Sci. USA. 2007;104:973–978
  67. Chiba T, Miyagi S, Saraya A, Aoki R, Seki A, Morita Y, et al. The polycomb gene product BMI1 contributes to the maintenance of tumor-initiating side population cells in hepatocellular carcinoma. Cancer Res. 2008;68:7742–7749
  68. Sasaki M, Ikeda H, Itatsu K, Yamaguchi J, Sawada S, Minato H, et al. The overexpression of polycomb group proteins Bmi1 and EZH2 is associated with the progression and aggressive biological behavior of hepatocellular carcinoma. Lab. Invest. 2008;88:873–882
  69. Collado M, Blasco MA, Serrano M. Cellular senescence in cancer and aging. Cell. 2007;130:223–233
  70. Reya T, Clevers H. Wnt signalling in stem cells and cancer. Nature. 2005;434:843–850
  71. Wei Y, Fabre M, Branchereau S, Gauthier F, Perilongo G, Buendia MA, et al. Activation of beta-catenin in epithelial and mesenchymal hepatoblastomas. Oncogene. 2000;19:498–504
  72. Cairo S, Armengol C, De Reyniès A, Wei Y, Thomas E, Renard CA, et al. Hepatic stem-like phenotype and interplay of Wnt/beta-catenin and Myc signaling in aggressive childhood liver cancer. Cancer Cell. 2008;14:471–484
  73. Mishra L, Shetty K, Tang Y, Stuart A, Byers SW. The role of TGF-beta and Wnt signaling in gastrointestinal stem cells and cancer. Oncogene. 2005;24:5775–5789
  74. Tang Y, Kitisin K, Jogunoori W, Li C, Deng CX, Mueller SC, et al. Progenitor/stem cells give rise to liver cancer due to aberrant TGF-beta and IL-6 signaling. Proc. Natl. Acad. Sci. USA. 2008;105:2445–2450
  75. Visvader JE, Lindeman GJ. Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nat. Rev. Cancer. 2008;8:755–768
  76. Higgins CF. Multiple molecular mechanisms for multidrug resistance transporters. Nature. 2007;446:749–757
  77. Haraguchi N, Utsunomiya T, H Inoue, Tanaka F, Mimori K, Barnard GF, et al. Characterization of a side population of cancer cells from human gastrointestinal system. Stem Cells. 2006;24:506–513
  78. Ishikawa F, Yoshida S, Saito Y, Hijikata A, Kitamura H, Tanaka S, et al. Chemotherapy-resistant human AML stem cells home to and engraft within the bone-marrow endosteal region. Nat. Biotechnol. 2007;25:1315–1321
  79. Kamohara Y, Haraguchi N, Mimori K, Tanaka F, Inoue H, Mori M, et al. The search for cancer stem cells in hepatocellular carcinoma. Surgery. 2008;144:144 119–124
  80. Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB, et al. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature. 2006;444:756–760
  81. Viale A, De Franco F, Orleth A, Cambiaghi V, Giuliani V, Bossi D, et al. Cell-cycle restriction limits DNA damage and maintains self-renewal of leukaemia stem cells. Nature. 2009;457:51–56
  82. Qin LF, Ng IO, Fan ST, Ng M. p21/WAF1, p53 and PCNA expression and p53 mutation status in hepatocellular carcinoma. Int. J. Cancer. 1998;79:424–428
  83. Ito K, Bernardi R, Morotti A, Matsuoka S, Saglio G, Ikeda Y, et al. PML targeting eradicates quiescent leukaemia-initiating cells. Nature. 2008;453:1072–1078
  84. Ma S, Lee TK, Zheng BJ, Chan KW, Guan XY. CD133+ HCC cancer stem cells confer chemoresistance by preferential expression of the Akt/PKB survival pathway. Oncogene. 2008;27:1749–1758
  85. Ma S, Lee TK, Zheng BJ, Chan KW, Guan XY. Characterization of cells with a high aldehyde dehydrogenase activity from cord blood and acute myeloid leukemia samples. Stem Cells. 2005;23:752–760
  86. Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M, et al. ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell. 2007;1:555–567
  87. Ma S, Chan KW, Lee TK, Tang KH, Wo JY, Zheng BJ, et al. Aldehyde dehydrogenase discriminates the CD133 liver cancer stem cell populations. Mol. Cancer Res. 2008;6:1146–1153
  88. Piccirillo SG, Reynolds BA, Zanetti N, Lamorte G, Binda E, Broggi G, et al. Bone morphogenetic proteins inhibit the tumorigenic potential of human brain tumour-initiating cells. Nature. 2006;444:761–765
  89. Shachaf CM, Kopelman AM, Arvanitis C, Karlsson A, Beer S, Mandl S, et al. MYC inactivation uncovers pluripotent differentiation and tumour dormancy in hepatocellular cancer. Nature. 2004;431:1112–1117
  90. Parviz F, Matullo C, Garrison WD, Savatski L, Adamson JW, Ning G, et al. Hepatocyte nuclear factor 4alpha controls the development of a hepatic epithelium and liver morphogenesis. Nat. Genet. 2003;34:292–296
  91. Yin C, Lin Y, Zhang X, Chen YX, Zeng X, Yue HY, et al. Differentiation therapy of hepatocellular carcinoma in mice with recombinant adenovirus carrying hepatocyte nuclear factor-4alpha gene. Hepatology. 2008;48:1528–1539
  92. Lim R, Knight B, Patel K, McHutchison JG, Yeoh GC, Olynyk JK. Antiproliferative effects of interferon alpha on hepatic progenitor cells in vitro and in vivo. Hepatology. 2006;43:1074–1083
  93. Cheson BD, Leonard JP. Monoclonal antibody therapy for B-cell non-Hodgkin’s lymphoma. New Engl. J. Med. 2008;359:613–626
  94. Jin L, Hope KJ, Zhai Q, Smadja-Joffe F, Dick JE. Targeting of CD44 eradicates human acute myeloid leukemic stem cells. Nat. Med. 2006;12:1167–1174
  95. Calabrese C, Poppleton H, Kocak M, Hogg TL, Fuller C, Hamner B, et al. A perivascular niche for brain tumor stem cells. Cancer Cell. 2007;11:69–82
  96. Thomas MB, Morris JS, Chadha R, Iwasaki M, Kaur H, Lin E, et al. Phase II trial of the combination of bevacizumab and erlotinib in patients who have advanced hepatocellular carcinoma. J. Clin. Oncol. 2009;27:843–850
  97. Kelly PN, Dakic A, Adams JM, Nutt SL, Strasser A, et al. Tumor growth need not be driven by rare cancer stem cells. Science. 2007;317:337

PII: S0304-3835(09)00304-8

doi: 10.1016/j.canlet.2009.04.027

Cancer Letters
Volume 286, Issue 2 , Pages 145-153 , 28 December 2009