Cancer stem cells: 20 years behind

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access


The biology of cancer stem cells (CSC) has been investigated and debated for past 20 years. Owning to their exceptional plasticity and the complexity of controlled processes CSC inspire the development of new research techniques for cell isolation and targeted therapy. This review is an attempt to summarize recent data and trends in the field of cancer stem cells and discuss potential and weaknesses of new research techniques

Full Text

Restricted Access

About the authors

R. N Mingaleeva

Kazan (Volga region) Federal University


R. R Miftakhova

Kazan (Volga region) Federal University

A. A Rizvanov

Kazan (Volga region) Federal University


  1. Clarke M.F., Dick J.F., Dirks P.B. et al. Cancer stem cells-perspectives on current status and future directions: AACR Workshop on cancer stem cells. Cancer Res. 2006; 66(19): 9339-44.
  2. Shiozawa Y., Nie B., Pienta K.J. et al. Cancer stem cells and their role in metastasis. Pharmacology & Therapeutics 2013; 138(2): 285-93
  3. Rosen J.M., Jordan C.T. The increasing complexity of the cancer stem cell paradigm. Science 2009; 324(5935): 1670-73.
  4. Van Rhenen A., Feller N., Kelder A. et al. High stem cell frequency in acute myeloid leukemia at diagnosis predicts high minimal residual disease and poor survival. Clin. Cancer Res. 2005; 11(18): 6520-6527
  5. Di Tomaso T., Mazzoleni S., Wang E. et al. Immunobiological characterization of cancer stem cells isolated from glioblastoma patients. Clin. Cancer Res. 2010; 16(3): 800-13.
  6. Shiozawa Y., Pedersen E., Havens A.M. et al. Human prostate cancer metastases target the hematopoietic stem cell niche to establish footholds in mouse bone marrow. J. Clin. Invest. 2011; 121(4): 1298-312.
  7. Borovski T., De Sousa E., Melo F. et al. Cancer stem cell niche: the place to be. Cancer Res. 2011; 71(3): 634-9.
  8. Lapidot T., Sirard C., Vormoor J. et al. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature 1994; 367(6464): 645-8.
  9. Quintana E., Shackleton M., Sabel M.S. et al. Efficient tumour formation by single human melanoma cells. Nature 2008; 456(7222): 593-598
  10. Лисяный Н.И., Лисяный А.Н. Стволовые опухолевые клетки злокачественных глиальных опухолей мозга. Онкология 2010; 12(3): 229-36.
  11. Tirino V., Desiderio V., Paino F. et al. Cancer stem cells in solid tumors: an overview and new approaches for their isolation and characterization. FASEB J 2013; 27(1): 13-24
  12. Scheel C., Eaton E.N., Li S.H. et al. Paracrine and autocrine signals induce and maintain mesenchymal and stem cell states in the breast. Cell 2011; 145(6): 926-40.
  13. Mani S.A., Guo W., Liao M.J. et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 2008; 133(4): 704-15.
  14. Shang Y., Cai X., Fan D. Roles of epithelial-mesenchymal transition in cancer drug resistance. Curr. Cancer Drug Targ. 2013; 13(9): 915-29.
  15. Zhou J., Zhang Y. Cancer stem cells: models, mechanisms and implications for improved treatment. Cell Cycle 2008; 7(10): 1360-70.
  16. Fabian A., Vereb G., Szollosi J. The hitchhikers guide to cancer stem cell theory: markers, pathways and therapy. Cytometry A 2013; 83(1): 62-71.
  17. Keysar S.B., Jimeno A., More than markers: biological significance of cancer stem cell-defining molecules. Mol. Cancer Ther. 2010; 9(9): 2450-7.
  18. Medema J.P., Cancer stem cells: the challenges ahead. Nat. Cell Biol. 2013; 15(4): 338-44.
  19. Magee J.A., Piskounova E., Morrison S.J. Cancer stem cells: impact, heterogeneity, and uncertainty. Cancer Cell 2012; 21(3): 283-96
  20. Marcato P., Dean C.A., Giacomantonio C.A. et al. Aldehyde dehydrogenase: its role as a cancer stem cell marker comes down to the specific isoform. Cell Cycle 2011; 10(9): 1378-84.
  21. Chumsri S., Shah P. Radiation resistance of cancer stem cells as an obstacle in cancer therapy. Mol. Cell Pharmacol. 2013; 5(1): 39-49
  22. Lou H., Dean M., Targeted therapy for cancer stem cells: the patched pathway and ABC transporters. Oncogene 2007; 26(9): 1357-60.
  23. Szakacs G., Annereau J.P., Lababidi S. et al. Predicting drug sensitivity and resistance: profiling ABC transporter genes in cancer cells. Cancer Cell 2004; 6(2): 129-37.
  24. Liu K., Lin B., Zhao M. et al. The multiple roles for Sox2 in stem cell maintenance and tumorigenesis. Cell Signal 2013; 25(5): 1264-71
  25. Bass A.J., Watanabe H., Mermel C.H. et al. SOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomas. Nat. Genet. 2009; 41(11): 1238-42.
  26. Basu-Roy U., Seo E., Ramanathapuram L. et al. Sox2 maintains self renewal of tumor-initiating cells in osteosarcomas. Oncogene 2012; 31(18): 2270-82.
  27. Boumahdi S., Driessens G., Lapouge G. et al. SOX2 controls tumour initiation and cancer stem-cell functions in squamous-cell carcinoma. Nature 2014; 511(7508): 246-50.
  28. Liu K., Jiang M., Lu Y. et al. Sox2 cooperates with inflammationmediated Stat3 activation in the malignant transformation of foregut basal progenitor cells. Cell Stem Cell 2013; 12(3): 304-15.
  29. Schoenhals M., Kassambara A., De Vos J. et al. Embryonic stem cell markers expression in cancers. Biochem. Biophys. Res. Commun. 2009; 383(2): 157-62.
  30. Kumar S.M., Liu S., Lu H. et al. Acquired cancer stem cell phenotypes through Oct4-mediated dedifferentiation. Oncogene 2012; 31(47): 4898-911.
  31. Linn D.E., Yang X., Sun F. et al. A role for OCT4 in tumor initiation of drug-resistant prostate cancer cells. Genes & Cancer 2010; 1(9): 908 -16.
  32. Chiou S.H., Wang M.L., Chou Y. T. et al. Coexpression of Oct4 and Nanog enhances malignancy in lung adenocarcinoma by inducing cancer stem cell-like properties and epithelial-mesenchymal transdifferentiation. Cancer Res. 2010; 70(24): 10433-44.
  33. Espinoza I., Pochampally R., Xing F. et al. Notch signaling: targeting cancer stem cells and epithelial-to-mesenchymal transition. Onco Targets Ther. 2013; 6: 1249-59.
  34. Kim Y., Kahn M. The role of the wnt signaling pathway in cancer stem cells: prospects for drug development. Res. Repor. Biochem. 2014; 4: 1-12.
  35. Anastas J.N., Moon R.T. WNT signalling pathways as therapeutic targets in cancer. Nat. Rev. Cancer 2013; 13(1): 11-26.
  36. Coni S., Infante P., Gulino A. Control of stem cells and cancer stem cells by Hedgehog signaling: pharmacologic clues from pathway dissection. Biotech. Pharmacol. 2013; 85(5): 623-8.
  37. Zhao C., Chen A., Jamieson C.H. et al. Hedgehog signalling is essential for maintenance of cancer stem cells in myeloid leukaemia. Nature 2009; 458(7239): 776-9.
  38. Merchant A.A., Matsui W., Targeting Hedgehog - a cancer stem cell pathway. Clin. Cancer Res. 2010; 16(12): 3130-40.
  39. Blatt N.L., Mingaleeva R.N., Khaiboullina S. F. et al. In vivo screening models of anticancer drugs. Life Sci. J. 2013; 10(4): 1892-900.
  40. Мингалеева Р.Н., Соловьева В.В., Блатт Н.Л. и др. Применение культур клеток и тканей для скрининга противоопухолевых препаратов in vitro. Клеточная трансплантология и тканевая инженерия 2013; 8(2): 20-8.
  41. Blatt N.L., Mingaleeva R. N., Solovieva V.V. et al. Application of cell and tissue culture systems for anticancer drug screening. WASJ 2013; 23(3): 315-25.
  42. Reya T., Morrison S.J., Clarke M.F. et al. Stem cells, cancer, and cancer stem cells. Nature 2001; 414(6859): 105-11.
  43. Gupta P.B., Onder T.T., Jiang G. et al. Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell 2009; 138(4): 645-59.
  44. Smith K.M., Datti A., Fujitani M. et al. Selective targeting of neuroblastomatumour-initiating cells by compounds identifiedin stem cell-based small molecule screens. EMBO Mol. Med. 2010; 2(9): 371-84.
  45. Smith L.M., Nesterova A., Ryan M.C. et al. CD133/prominin-1 is a potential therapeutic target for antibody-drug conjugates in hepatocellular and gastric cancers. Br. J. Cancer 2008; 99(1): 100-9.
  46. Jin L., Hope K.J., Zhai Q. et al. Targeting of CD44 eradicates human acute myeloid leukemic stem cells. Nat. Med. 2006; 12(10): 1167-74.
  47. Pol J., Bloy N., Obrist F. et al. Trial watch: oncolytic viruses for cancer therapy. Oncoimmunology 2014; 3: e28694.
  48. Kanerva A., Nokisalmi P., Diaconu I. et al. Antiviral and antitumor T-cell immunity in patients treated with GM-CSF-coding oncolytic adenovirus. Clin. Cancer Res. 2013; 19(10): 2734-44.
  49. Yano S., Tazawa H., Hashimoto Y. A genetically engineered oncolytic adenovirus decoys and lethally traps quiescent cancer stem-like cells in S/G2/M phases. Clin. Cancer Res. 2013; 19(23): 6495-505
  50. Kono K., Current status of cancer immunotherapy. J. Stem Cells Regen. Med. 2014; 10(1): 8-13.
  51. Kochenderfer J.N., Yu Z., Frasheri D. et al. Adoptive transfer of syngeneic T-cells transduced with a chimeric antigen receptor that recognizes murine CD19 can eradicate lymphoma and normal B cells. Blood 2010; 116(19): 3875-86.
  52. Ponnusamy M.P., Batra S.K. Ovarian cancer: emerging concept on cancer stem cells. J. Ovarian. Res. 2008; 1: 4.
  53. Ma W., Ma J., Xu J. et al. Lin28 regulates BMP4 and functions with Oct4 to affect ovarian tumor microenvironment. Cell Cycle 2013; 12(1): 88-97.
  54. Penumatsa K., Edassery S.L., Barua A. et al. Differential expression of aldehyde dehydrogenase 1a1 (ALDH1) in normal ovary and serous ovarian tumors. J. Ovarian. Res. 2010; 3(28): 28.
  55. Collins A.T., Berry P.A., Hyde C. et al. Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res. 2005; 65(23): 10946-51.
  56. Rybak A.P., Tang D., SOX2 plays a critical role in EGFR-mediated self-renewal of human prostate cancer stem-like cells. Cell Signal 2013; 25(12): 2734-42.
  57. Eramo A., Lotti F., Sette G. et al. Identification and expansion of the tumorigenic lung cancer stem cell population. Cell Death Differ. 2007; 15(3): 504-14.
  58. Jiang F., Qiu Q., Khanna A. et al. Aldehyde dehydrogenase 1 is a tumor stem cell-associated marker in lung cancer. Mol. Cancer Res. 2009; 7(3): 330-8.
  59. Ucar D., Cogle C.R., Zucali J.R. et al. Aldehyde dehydrogenase activity as a functional marker for lung cancer. Chem. Biol. Interact. 2009; 178(1-3): 48-55.
  60. Chen K., Huang Y.-H., Chen J.-l. Understanding and targeting cancer stem cells: therapeutic implications and challenges. Acta Pharmacol. Sin. 2013; 34(6): 732-40.
  61. Klonisch T., Wiechec E., Hombach-Klonisch S. et al. Cancer stem cell markers in common cancers - therapeutic implications. Trends Mol. Med. 2008; 14(10): 450-60.
  62. Ginestier C., Hur M.H., 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 Cell 2007; 1(5): 555-67.
  63. Liu C.G., Lu Y., Wang B.B. et al. Clinical implications of stem cell gene Oct-4 expression in breast cancer. Ann Surg. 2011; 253(6): 1165-71
  64. Lee C.J., Dosch J., Simeone D.M. Pancreatic cancer stem cells. J. Clin. Oncol. 2008. 26(17): 2806-12.
  65. Herreros-Villanueva M., Zhang J.S., Koenig, A. et al. SOX2 promotes dedifferentiation and imparts stem cell-like features to pancreatic cancer cells. Oncogenesis 2013; 2: e61.
  66. Lu Y., Zhu H., Shan H. et al. Knockdown of Oct4 and Nanog expression inhibits the stemness of pancreatic cancer cells. Cancer Lett. 2013; 340(1): 113-23.
  67. Dalerba P., Dylla S.J., Park I.K. et al. Phenotypic characterization of human colorectal cancer stem cells. PNAS USA 2007; 104(24): 10158-63.
  68. O'Brien C.A., Pollett A., Gallinger S. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 2007; 445(7123): 106-10.
  69. Huang E.H., Hynes M.F., Zhang T. et al. Aldehyde dehydrogenase 1 is a marker for normal and malignant human colonic stem cells (SC) and tracks SC overpopulation during colon tumorigenesis. Cancer Res. 2009; 69(8): 3382-9.
  70. Guzman M.L., Jordan C.T. Considerations for targeting malignant stem cells in leukemia. Cancer Control. 2004; 11(2): 97-104.
  71. Zhou W., Yang Y., Gu Z. et al. ALDH1 activity identifies tumor-initiating cells and links to chromosomal instability signatures in multiple myeloma. Leukemia 2014; 28(5): 1155-8.

Copyright (c) 2015 Eco-Vector

СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: ПИ № ФС 77 - 85657 от 21.07.2023 от 11.03.2014.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies