Skip to main content

Advertisement

SpringerLink
Log in

Properties and identification of cancer stem cells: A changing insight into intractable cancer

  • Review Article
  • Published:
Surgery Today Aims and scope Submit manuscript

Abstract

Although the idea was originally proposed decades ago, it has recently emerged that cancer can arise from small cell populations that differ from other progenies. These populations have the ability not only to renew themselves, but also to give rise to diverse phenotypes through the process of differentiation. The result is the formation of clinically observed heterogeneous tumors. Because of their similarity to somatic stem cells, these small cell populations have been termed cancer stem cells (CSCs). The involvement of CSCs was demonstrated in leukemia and has since been noted in other solid tumors, such as brain, breast, and gastrointestinal cancers. We support the notion that a curative operation serves as the most beneficial means to make a prognosis of malignancies. However, currently, chemotherapy is another of the promising strategies for the successful treatment of some malignancies. It is thought, however, that CSCs play a role in resistance to anticancer therapy, thus leading to the occurrence of metastasis, a common characteristic of intractable tumors. As a result, the study of CSCs is expected to improve the effectiveness of current therapies and lead to the development of novel therapeutic approaches for such cancers in the future.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Pardal R, Clarke MF, Morrison SJ. Applying the principles of stem-cell biology to cancer. Nature Rev Cancer 2003;3:895–902.

    Article  CAS  Google Scholar 

  2. Reya, T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature 2001;414:105–111.

    Article  CAS  PubMed  Google Scholar 

  3. Hamburger AW, Salmon SE. Primary bioassay of human tumor stem cells. Science 1997;29:461–463.

    Google Scholar 

  4. Lapidot T, Sirard C, Vormoor J, Murdch B, Hoang T, Caceres-Cortes J, et al. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature 1994;367:645–648.

    Article  CAS  PubMed  Google Scholar 

  5. 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.

    Article  CAS  PubMed  Google Scholar 

  6. 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.

    Article  CAS  PubMed  Google Scholar 

  7. Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, et al. Identification of human brain tumour initiating cells. Nature 2004;432:396–401.

    Article  CAS  PubMed  Google Scholar 

  8. 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.

    Article  CAS  PubMed  Google Scholar 

  9. Kim CF, Jackson EL, Woolfenden AE, Lawrence S, Barbar I, Vogel S, et al. Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell 2005;121:823–835.

    Article  CAS  PubMed  Google Scholar 

  10. Wang S, Garcia AJ, Wu M, Lawson DA, Witte ON, Wu H. Pten deletion leads to the expansion of a prostatic stem/progenitor cell subpopulation and tumor initiation. Proc Natl Acad Sci USA 2006;103:1480–1485.

    Article  CAS  PubMed  Google Scholar 

  11. Varnum-Finney B, Xu L, Brashem-Stein C, Nourigat C, Flowers D, Bakkour S, et al. Pluripotent, cytokine-dependent, hematopoietic stem cells are immortalized by constitutive Notch1 signaling. Nat Med 2000;6:1278–1281.

    Article  CAS  PubMed  Google Scholar 

  12. Karanu FN, Murdoch B, Gallacher L, Wu DM, Koremoto M, Sakano S, et al. The notch ligand jagged-1 represents a novel growth factor of human hematopoietic stem cells. J Exp Med 2000;192:1365–1372.

    Article  CAS  PubMed  Google Scholar 

  13. Berman DM, Karhadkar SS, Maitra A, Montes De Oca R, Gerstenblith MR, Briggs K, et al. Widespread requirement for hedgehog ligand stimulation in growth of digestive tract tumours. Nature 2003;425:846–851.

    Article  CAS  PubMed  Google Scholar 

  14. Mukherjee S, Frolova N, Sadlonova A, Novak Z, Steg A, Page GP, et al. Hedgehog signaling and response to cyclopamine differ in epithelial and stromal cells in benign breast and breast cancer. Cancer Biol Ther 2006;5:674–683.

    CAS  PubMed  Google Scholar 

  15. Bar EE, Chaudhry A, Lin A, Fan X, Schreck K, Matsui W, et al. Cyclopamine-mediated hedgehog pathway inhibition depletes stem-like cancer cells in glioblastoma. Stem Cells 2007;25:2524–2533.

    Article  CAS  PubMed  Google Scholar 

  16. Yang W, Yan HX, Chen L, Liu Q, He YQ, Yu LX, et al. Wnt/β-catenin signaling contributes to activation of normal and tumorigenic liver progenitor cells. Cancer Res 2008;68:4287–4295.

    Article  CAS  PubMed  Google Scholar 

  17. Sell S, Pierce GB. Maturation arrest of stem cell differentiation is a common pathway for the cellular origin of teratocarcinomas and epithelial cancers. Lab Invest 1994;70:6–22.

    CAS  PubMed  Google Scholar 

  18. Sawyers CL, Denny CT, Witte ON. Leukemia and the disruption of normal hematopoiesis. Cell 1991;64:337–350.

    Article  CAS  PubMed  Google Scholar 

  19. Reddy GP, Tiarks CY, Pang L, Wuu J, Hsieh CC, Quesenberry PJ. Cell cycle analysis and synchronization of pluripotent hematopoietic progenitor stem cells. Blood 1997;90:2293–2299.

    CAS  PubMed  Google Scholar 

  20. Guzman ML, Swiderski CF, Howard DS, Grimes BA, Rossi RM, Szilvassy SJ, et al. Preferential induction of apoptosis for primary human leukemic stem cells. Proc Natl Acad Sci USA 2002;99:16220–16225.

    Article  CAS  PubMed  Google Scholar 

  21. Jedema I, Barge RM, Frankel AE, Willemze R, Falkenburg JH. Acute myeloid leukemia cells in G0 phase of the cell cycle that are unresponsive to conventional chemotherapy are sensitive to treatment with granulocyte-macrophage colony-stimulating factor/diphtheria toxin fusion proteins. Exp Hematol 2004;32:188–194.

    Article  CAS  PubMed  Google Scholar 

  22. Krause DS, Lazarides K, von Andrian UH, Van Etten RA. Requirement for CD44 in homing and engraftment of BCRABL-expressing leukemic stem cells. Nat Med 2006;12:1175–1180.

    Article  CAS  PubMed  Google Scholar 

  23. Fillmore CM, Kuperwasser C. Human breast cancer cell lines contain stem-like cells that self-renew, give to phenotypically diverse progeny and survive chemotherapy. Breast Cancer Res 2008;10:R25.

    Article  PubMed  Google Scholar 

  24. Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J, et al. Identification of a cancer stem cell on human brain tumors. Cancer Res 2003;63:5821–5828.

    CAS  PubMed  Google Scholar 

  25. Beier D, Hau P, Proescholdt M, Lohmeier A, Wischhusen J, Oefner PJ, et al. CD133(+) and CD133(−) glioblastoma-derived cancer stem cells show differential growth characteristics and molecular profiles. Cancer Res 2007;67:4010–4015.

    Article  CAS  PubMed  Google Scholar 

  26. 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.

    Article  CAS  PubMed  Google Scholar 

  27. 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.

    Article  CAS  PubMed  Google Scholar 

  28. 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.

    Article  CAS  PubMed  Google Scholar 

  29. 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.

    Article  CAS  PubMed  Google Scholar 

  30. Li C, Heidt DG, Dalerba P, Burant CF, Zhang L, Adsay V, et al. Identification of pancreatic cancer stem cells. Cancer Res 2007;67:1030–1037.

    Article  CAS  PubMed  Google Scholar 

  31. Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C, et al. Identification and expansion of human coloncancer-initiating cells. Nature 2007;445:111–115.

    Article  CAS  PubMed  Google Scholar 

  32. O’Brien CA, Pollett A, Gallinger S, Dick JE. A human colon cancer capable of initiating tumour growth in immunodeficient mice. Nature 2007;445:106–110.

    Article  PubMed  Google Scholar 

  33. Du L, Wang H, He L, Zhang J, Ni B, Wang X, et al. CD44 is of functional importance for colorectal cancer stem cells. Clin Cancer Res 2008;14:6751–6760.

    Article  CAS  PubMed  Google Scholar 

  34. Kasper S. Exploring the origins of the normal prostate and prostate cancer stem cell. Stem Cell Rev 2008;4:193–201.

    Article  CAS  PubMed  Google Scholar 

  35. Collins AT, Berry PA, Hyde C, Stower MJ, Maitland NJ. Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res 2005;65:10946–10951.

    Article  CAS  PubMed  Google Scholar 

  36. Zabierowski SE, Herlyn M. Melanoma stem cells: the dark seed of melanoma. J Clin Oncol 2008;26:2890–2894.

    Article  PubMed  Google Scholar 

  37. Carpenter MK, Rosler E, Rao MS. Characterization and differentiation of human embryonic stem cells. Cloning Stem Cells 2003;5:79–88.

    Article  CAS  PubMed  Google Scholar 

  38. International Stem Cell Initiative, Adewumi O, Aflatoonian B, Ahrlund-Richter L, Amit M, Andrews PW, et al. Characterization of human embryonic stem cell lines by the International Stem Cell Initiative. Nat Biotechnol 2007;25:803–816.

    Article  CAS  PubMed  Google Scholar 

  39. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 2007;131:861–872.

    Article  CAS  PubMed  Google Scholar 

  40. McCulloch EA, Curtis JE, Messner HA, Senn JS, Germanson TP. The contribution of blast cell properties to outcome variation in acute myeloblastic leukemia (AML). Blood 1982;59:601–608.

    CAS  PubMed  Google Scholar 

  41. Grogan TM, Spier CM, Salmon SE, Matzner M, Rybski J, Weinstein RS, et al. P-glycoprotein expression in human plasma cell myeloma: Correlation with prior chemotherapy. Blood 1993;81:490–495.

    CAS  PubMed  Google Scholar 

  42. Belpomme D, Gauthier S, Pujade-Lauraine E, Facchini T, Goudier MJ, Krakowski I, et al. Verapamil increases the survival of patients with anthracycline-resistant metastatic breast carcinoma. Ann Oncol 2000;11:1471–1476.

    Article  CAS  PubMed  Google Scholar 

  43. Wulf GG, Wang RY, Kuehnle I, Weidner D, Marini F, Brenner MK, et al. A leukemic stem cell with intrinsic drug efflux capacity in acute myeloid leukemia. Blood 2001;98:1166–1173.

    Article  CAS  PubMed  Google Scholar 

  44. Kawabata S, Oka M, Soda H, Shiozawa K, Nakatomi K, Tsurutani J, et al. Expression and functional analyses of breast cancer resistance protein in lung cancer. Clin Cancer Res 2003;9:3052–3057.

    CAS  PubMed  Google Scholar 

  45. O’Brien SG, Guilhot F, Larson RA, Gathmann I, Baccarani M, Cervantes F, et al. Imatinib compared with interferon and lowdose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 2003;13:994–1004.

    Article  Google Scholar 

  46. Yasui K, Mihara S, Zhao C, Okamoto H, Saito-Ohara F, Tomida A, et al. Alteration in copy numbers of genes as a mechanism for acquired drug resistance. Cancer Res 2004;64:1403–1410.

    Article  CAS  PubMed  Google Scholar 

  47. 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.

    Article  CAS  PubMed  Google Scholar 

  48. 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.

    Article  CAS  PubMed  Google Scholar 

  49. Haraguchi N, Utsunomiya T, Inoue H, 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.

    Article  CAS  PubMed  Google Scholar 

  50. Hahn WC, Weinberg RA. Rules for making human tumor cells. N Engl J Med 2002;347:1593–1603.

    Article  CAS  PubMed  Google Scholar 

  51. Egger G, Liang G, Aparicio A, Jones PA. Epigenetics in human disease and prospects for epigenetic therapy. Nature 2004;429:457–463.

    Article  CAS  PubMed  Google Scholar 

  52. Yoshino I, Maehara Y. Impact of smoking status on the biological behavior of lung cancer. Surg Today 2007;37:725–734.

    Article  PubMed  Google Scholar 

  53. Felsher DW. Cancer revoked: oncogenes as therapeutic targets. Nat Rev Cancer 2003;3:375–380.

    Article  CAS  PubMed  Google Scholar 

  54. Liu S, Dontu G, Mantle ID, Patel S, Ahn NS, Jackson KW, et al. Hedgehog signaling and Bmi-1 regulate self-renewal of normal and malignant human mammary stem cells. Cancer Res 2006;66:6063–6071.

    Article  CAS  PubMed  Google Scholar 

  55. Park IK, Qian D, Kiel M, Becker MW, Pihalja M, Weissman IL, et al. Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells. Nature 2003;423:302–305.

    Article  CAS  PubMed  Google Scholar 

  56. Wilmut I, Schnieke AE, McWhir J, Kind AJ, Campbell KH. Viable offspring derived from fetal and adult mammalian cells. Nature 1997;385:810–813.

    Article  CAS  PubMed  Google Scholar 

  57. Wakayama T, Perry AC, Zuccotti M, Johnson KR, Yanagimachi R. Full-term development of mice from enucleated oocytes injected with cumulus cell nuclei. Nature 1998;394:369–374.

    Article  CAS  PubMed  Google Scholar 

  58. Lou H, Dean M. Targeted therapy for cancer stem cells: the patched pathway and ABC transporters. Oncogene 2007;26:1357–1360.

    Article  CAS  PubMed  Google Scholar 

  59. Ponti D, Costa A, Zaffaroni N, Pratesi G, Petrangolini G, Coradini D, et al. Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/progenitor cell properties. Cancer Res 2005;65:5506–5511.

    Article  CAS  PubMed  Google Scholar 

  60. Yuan X, Curtin J, Xiong Y, Liu G, Waschsmann-Hogiu S, Farkas DL, et al. Isolation of cancer stem cells from adult glioblastoma multiforme. Oncogene 2004;23:9392–9400.

    Article  CAS  PubMed  Google Scholar 

  61. Patrawala L, Calhoun T, Schneider-Broussard R, Li H, Bhatia B, Tang S, et al. Highly purified CD44+ prostate cancer cells from xenograft human tumors are enriched in tumorigenic and metastatic progenitor cells. Oncogene 2006;25:1696–1708.

    Article  CAS  PubMed  Google Scholar 

  62. Miki J, Furusato B, Li H, Gu Y, Takahashi H, Egawa S, et al. Identification of putative stem cell markers, CD133 and CXCR4, in hTERT-immortalized primary nonmalignant and malignant tumor-derived human prostate epithelial cell lines and in prostate cancer specimens. Cancer Res 2007;67:315331–61.

    Google Scholar 

  63. Houghton J, Stoicov C, Nomura S, Rogers AB, Carlson J, Li H, et al. Gastric cancer originating from bone marrow-derived cells. Science 2004;306:1568–1571.

    Article  CAS  PubMed  Google Scholar 

  64. Sakaida I. Clinical application of bone marrow cell transplantation for liver diseases. J Gastroenterol 2006;41:93–94.

    Article  PubMed  Google Scholar 

  65. Cao H, Xu W, Qian H, Zhu W, Yan Y, Zhou H, et al. Mesenchymal stem cell-like cells derived from human gastric cancer tissues. Cancer Lett 2009;274:61–71.

    Article  CAS  PubMed  Google Scholar 

  66. Zheng JF, Liang LJ. Transplanted bone marrow stromal cells are not cellular origin of hepatocellular carcinomas in a mouse model of carcinogenesis. World J Gastroenterol 2008;14:3015–3020.

    Article  PubMed  Google Scholar 

  67. Beckermann BM, Kallifatidis G, Groth A, Frommhold D, Apel A, Mattern J, et al. VEGF expression by mesenchymal stem cells contributes to angiogenesis in pancreatic carcinoma. Br J Cancer 2008;99:622–631.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Norikatsu Miyoshi, Hideshi Ishii, Mitsugu Sekimoto, Naotsugu Haraguchi, Yuichiro Doki & Masaki Mori

Authors
  1. Norikatsu Miyoshi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hideshi Ishii
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mitsugu Sekimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Naotsugu Haraguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yuichiro Doki
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Masaki Mori
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Miyoshi, N., Ishii, H., Sekimoto, M. et al. Properties and identification of cancer stem cells: A changing insight into intractable cancer. Surg Today 40, 608–613 (2010). https://doi.org/10.1007/s00595-009-4106-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00595-009-4106-6

Key words

Search

Navigation