International Journal of Cancer Management

Published by: Kowsar

Cancer Stem Cell’s Potential Clinical Implications

Alireza Mirzaei 1 , 2 , * , Zahra Madjd 3 , 4 , Azade Amini Kadijani 5 , Samaneh Alinaghi 5 , Abolfazl Akbari 6 and Gholamreza Tavoosidana 1
Authors Information
1 Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
2 Bone and Joint Reconstruction Research Center, Shafa Orthopedic Hospital, Iran University of Medical Sciences, Tehran, Iran
3 Oncopathology Research Center, Iran University of Medical Sciences, Tehran, Iran
4 Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
5 Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
6 Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran
Article information
  • Iranian Journal of Cancer Prevention: January 2017, 10 (1); e5897
  • Published Online: January 23, 2017
  • Article Type: Review Article
  • Received: March 7, 2016
  • Revised: June 6, 2016
  • Accepted: January 3, 2017
  • DOI: 10.17795/ijcp-5897

To Cite: Mirzaei A, Madjd Z, Amini Kadijani A, Alinaghi S, Akbari A, et al. Cancer Stem Cell’s Potential Clinical Implications, Int J Cancer Manag. 2017 ; 10(1):e5897. doi: 10.17795/ijcp-5897.

Copyright © 2017, Iranian Journal of Cancer Prevention. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License ( which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.
1. Context
2. Evidence Acquisition
3. Results
4. Conclusions
  • 1. Lobo NA, Shimono Y, Qian D, Clarke MF. The biology of cancer stem cells. Annu Rev Cell Dev Biol. 2007; 23: 675-99[DOI][PubMed]
  • 2. Clevers H. The cancer stem cell: premises, promises and challenges. Nat Med. 2011; 17(3): 313-9[DOI][PubMed]
  • 3. Bonnet D, Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med. 1997; 3(7): 730-7[DOI][PubMed]
  • 4. Visvader JE, Lindeman GJ. Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nat Rev Cancer. 2008; 8(10): 755-68[DOI][PubMed]
  • 5. Gil J, Stembalska A, Pesz KA, Sasiadek MM. Cancer stem cells: the theory and perspectives in cancer therapy. J Appl Genet. 2008; 49(2): 193-9[DOI][PubMed]
  • 6. Bonito MD, Cantile M, Malzone G, Liguori G, Botti G. The prognostic role of cancer stem cells in breast tumors. J Clin Med Res. 2013; 5(5): 325-6[DOI][PubMed]
  • 7. Tang DG. Understanding cancer stem cell heterogeneity and plasticity. Cell Res. 2012; 22(3): 457-72[DOI][PubMed]
  • 8. Shackleton M. Normal stem cells and cancer stem cells: similar and different. Seminars in cancer biology. 2010;
  • 9. Natarajan TG, FitzGerald KT. Markers in normal and cancer stem cells. Cancer Biomark. 2007; 3(4-5): 211-31[PubMed]
  • 10. Mirzaei A, Tavoosidana G, Modarressi MH, Rad AA, Fazeli MS, Shirkoohi R, et al. Upregulation of circulating cancer stem cell marker, DCLK1 but not Lgr5, in chemoradiotherapy-treated colorectal cancer patients. Tumour Biol. 2015; 36(6): 4801-10[DOI][PubMed]
  • 11. Chen K, Huang YH, Chen JL. Understanding and targeting cancer stem cells: therapeutic implications and challenges. Acta Pharmacol Sin. 2013; 34(6): 732-40[DOI][PubMed]
  • 12. Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature. 2001; 414(6859): 105-11[DOI][PubMed]
  • 13. Hauswirth AW, Florian S, Printz D, Sotlar K, Krauth MT, Fritsch G, et al. Expression of the target receptor CD33 in CD34+/CD38-/CD123+ AML stem cells. Eur J Clin Invest. 2007; 37(1): 73-82[DOI][PubMed]
  • 14. Sperr WR, Florian S, Hauswirth AW, Valent P. CD 33 as a target of therapy in acute myeloid leukemia: current status and future perspectives. Leuk Lymphoma. 2005; 46(8): 1115-20[DOI][PubMed]
  • 15. ten Cate B, de Bruyn M, Wei Y, Bremer E, Helfrich W. Targeted elimination of leukemia stem cells; a new therapeutic approach in hemato-oncology. Curr Drug Targets. 2010; 11(1): 95-110[DOI][PubMed]
  • 16. ten Cate B, Bremer E, de Bruyn M, Bijma T, Samplonius D, Schwemmlein M, et al. A novel AML-selective TRAIL fusion protein that is superior to Gemtuzumab Ozogamicin in terms of in vitro selectivity, activity and stability. Leukemia. 2009; 23(8): 1389-97[DOI][PubMed]
  • 17. British Committee for Standards in H, Milligan DW, Grimwade D, Cullis JO, Bond L, Swirsky D, et al. Guidelines on the management of acute myeloid leukaemia in adults. Br J Haematol. 2006; 135(4): 450-74[DOI][PubMed]
  • 18. van Rhenen A, van Dongen GA, Kelder A, Rombouts EJ, Feller N, Moshaver B, et al. The novel AML stem cell associated antigen CLL-1 aids in discrimination between normal and leukemic stem cells. Blood. 2007; 110(7): 2659-66[DOI][PubMed]
  • 19. Smadja F, Dick J, Kadouche J. Chimeric Anti Cd44 Antibodies and Their Use for Treating Acute Myeloid Leukemia 2004;
  • 20. Pardal R, Clarke MF, Morrison SJ. Applying the principles of stem-cell biology to cancer. Nat Rev Cancer. 2003; 3(12): 895-902[DOI][PubMed]
  • 21. Bleau AM, Hambardzumyan D, Ozawa T, Fomchenko EI, Huse JT, Brennan CW, et al. PTEN/PI3K/Akt pathway regulates the side population phenotype and ABCG2 activity in glioma tumor stem-like cells. Cell Stem Cell. 2009; 4(3): 226-35[DOI][PubMed]
  • 22. Hoey T, Fischer M, Yen WC, Kapoun AM, Wang M, O'Young G, et al. Anti-DLL4 inhibits growth and reduces tumor-initiating cell frequency in colorectal tumors with oncogenic KRAS mutations. Cancer Res. 2011; 71(5): 1520-5[DOI][PubMed]
  • 23. Von Hoff DD, LoRusso PM, Rudin CM, Reddy JC, Yauch RL, Tibes R, et al. Inhibition of the hedgehog pathway in advanced basal-cell carcinoma. N Engl J Med. 2009; 361(12): 1164-72[DOI][PubMed]
  • 24. Weng D, Song B, Durfee J, Sugiyama V, Wu Z, Koido S, et al. Induction of cytotoxic T lymphocytes against ovarian cancer-initiating cells. Int J Cancer. 2011; 129(8): 1990-2001[DOI][PubMed]
  • 25. Brown CE, Starr R, Martinez C, Aguilar B, D'Apuzzo M, Todorov I, et al. Recognition and killing of brain tumor stem-like initiating cells by CD8+ cytolytic T cells. Cancer Res. 2009; 69(23): 8886-93[DOI][PubMed]
  • 26. Yu F, Yao H, Zhu P, Zhang X, Pan Q, Gong C, et al. let-7 regulates self renewal and tumorigenicity of breast cancer cells. Cell. 2007; 131(6): 1109-23[DOI][PubMed]
  • 27. Jiang P, Rao EY, Meng N, Zhao Y, Wang JJ. MicroRNA-17-92 significantly enhances radioresistance in human mantle cell lymphoma cells. Radiat Oncol. 2010; 5: 100[DOI][PubMed]
  • 28. Pece S, Tosoni D, Confalonieri S, Mazzarol G, Vecchi M, Ronzoni S, et al. Biological and molecular heterogeneity of breast cancers correlates with their cancer stem cell content. Cell. 2010; 140(1): 62-73[DOI][PubMed]
  • 29. Horst D, Kriegl L, Engel J, Kirchner T, Jung A. Prognostic significance of the cancer stem cell markers CD133, CD44, and CD166 in colorectal cancer. Cancer Invest. 2009; 27(8): 844-50[DOI][PubMed]
  • 30. Maeda S, Shinchi H, Kurahara H, Mataki Y, Maemura K, Sato M, et al. CD133 expression is correlated with lymph node metastasis and vascular endothelial growth factor-C expression in pancreatic cancer. Br J Cancer. 2008; 98(8): 1389-97[DOI][PubMed]
  • 31. Zhang J, Guo X, Chang DY, Rosen DG, Mercado-Uribe I, Liu J. CD133 expression associated with poor prognosis in ovarian cancer. Mod Pathol. 2012; 25(3): 456-64[DOI][PubMed]
  • 32. Qu H, Li R, Liu Z, Zhang J, Luo R. Prognostic value of cancer stem cell marker CD133 expression in non-small cell lung cancer: a systematic review. Int J Clin Exp Pathol. 2013; 6(11): 2644-50[PubMed]
  • 33. Guo Y, Kock K, Ritter CA, Chen ZS, Grube M, Jedlitschky G, et al. Expression of ABCC-type nucleotide exporters in blasts of adult acute myeloid leukemia: relation to long-term survival. Clin Cancer Res. 2009; 15(5): 1762-9[DOI][PubMed]
  • 34. Mima K, Okabe H, Ishimoto T, Hayashi H, Nakagawa S, Kuroki H, et al. CD44s regulates the TGF-beta-mediated mesenchymal phenotype and is associated with poor prognosis in patients with hepatocellular carcinoma. Cancer Res. 2012; 72(13): 3414-23[DOI][PubMed]
  • 35. Mulder JW, Kruyt PM, Sewnath M, Oosting J, Seldenrijk CA, Weidema WF, et al. Colorectal cancer prognosis and expression of exon-v6-containing CD44 proteins. Lancet. 1994; 344(8935): 1470-2[DOI][PubMed]
  • 36. Gotoda T, Matsumura Y, Kondo H, Saitoh D, Shimada Y, Kosuge T, et al. Expression of CD44 variants and its association with survival in pancreatic cancer. Jpn J Cancer Res. 1998; 89(10): 1033-40[DOI][PubMed]
  • 37. Chaffer CL, Weinberg RA. A perspective on cancer cell metastasis. Science. 2011; 331(6024): 1559-64[DOI][PubMed]
  • 38. Rao GC, Larson C, Repollet M, Rutner H, Terstappen LW, O'hara SM. Analysis of circulating tumor cells, fragments, and debris 2012;
  • 39. Pantel K, Brakenhoff RH. Dissecting the metastatic cascade. Nat Rev Cancer. 2004; 4(6): 448-56[DOI][PubMed]
  • 40. Yang ZF, Ngai P, Ho DW, Yu WC, Ng MN, Lau CK, et al. Identification of local and circulating cancer stem cells in human liver cancer. Hepatology. 2008; 47(3): 919-28[DOI][PubMed]
  • 41. Iinuma H, Watanabe T, Mimori K, Adachi M, Hayashi N, Tamura J, et al. Clinical significance of circulating tumor cells, including cancer stem-like cells, in peripheral blood for recurrence and prognosis in patients with Dukes' stage B and C colorectal cancer. J Clin Oncol. 2011; 29(12): 1547-55[DOI][PubMed]
  • 42. Pilati P, Mocellin S, Bertazza L, Galdi F, Briarava M, Mammano E, et al. Prognostic value of putative circulating cancer stem cells in patients undergoing hepatic resection for colorectal liver metastasis. Ann Surg Oncol. 2012; 19(2): 402-8[DOI][PubMed]
  • 43. Valladares-Ayerbes M, Blanco-Calvo M, Reboredo M, Lorenzo-Patino MJ, Iglesias-Diaz P, Haz M, et al. Evaluation of the adenocarcinoma-associated gene AGR2 and the intestinal stem cell marker LGR5 as biomarkers in colorectal cancer. Int J Mol Sci. 2012; 13(4): 4367-87[DOI][PubMed]
  • 44. Wang N, Shi L, Li H, Hu Y, Du W, Liu W, et al. Detection of circulating tumor cells and tumor stem cells in patients with breast cancer by using flow cytometry: a valuable tool for diagnosis and prognosis evaluation. Tumour Biol. 2012; 33(2): 561-9[DOI][PubMed]
  • 45. Hilakivi-Clarke L, de Assis S. Fetal origins of breast cancer. Trends Endocrinol Metab. 2006; 17(9): 340-8[DOI][PubMed]
  • 46. Wang Z, Zhang Y, Banerjee S, Li Y, Sarkar FH. Notch-1 down-regulation by curcumin is associated with the inhibition of cell growth and the induction of apoptosis in pancreatic cancer cells. Cancer. 2006; 106(11): 2503-13[DOI][PubMed]
  • 47. Jaiswal AS, Marlow BP, Gupta N, Narayan S. Beta-catenin-mediated transactivation and cell-cell adhesion pathways are important in curcumin (diferuylmethane)-induced growth arrest and apoptosis in colon cancer cells. Oncogene. 2002; 21(55): 8414-27[DOI][PubMed]
  • 48. Pahlke G, Ngiewih Y, Kern M, Jakobs S, Marko D, Eisenbrand G. Impact of quercetin and EGCG on key elements of the Wnt pathway in human colon carcinoma cells. J Agric Food Chem. 2006; 54(19): 7075-82[DOI][PubMed]
  • 49. Nagler A, Riklis I, Kletter Y, Tatarsky I, Fabian I. Effect of 1,25 dihydroxyvitamin D3 and retinoic acid on normal human pluripotent (CFU-mix), erythroid (BFU-E), and myeloid (CFU-C) progenitor cell growth and differentiation patterns. Exp Hematol. 1986; 14(1): 60-5[PubMed]
  • 50. Owens DK, Qaseem A, Chou R, Shekelle P, Clinical Guidelines Committee of the American College of P. High-value, cost-conscious health care: concepts for clinicians to evaluate the benefits, harms, and costs of medical interventions. Ann Intern Med. 2011; 154(3): 174-80[DOI][PubMed]
  • 51. Sylvester KG, Longaker MT. Stem cells: review and update. Arch Surg. 2004; 139(1): 93-9[DOI][PubMed]
  • 52. Avasthi S, Srivastava R, Singh A. Stem cell: past, present and future-a review article. Int J Med Update. 2008; 3(1)
  • 53. Soltysova A, Altanerova V, Altaner C. Cancer stem cells. Neoplasma. 2005; 52(6): 435-40[PubMed]
  • 54. Wong DJ, Liu H, Ridky TW, Cassarino D, Segal E, Chang HY. Module map of stem cell genes guides creation of epithelial cancer stem cells. Cell Stem Cell. 2008; 2(4): 333-44[DOI][PubMed]
  • 55. Karsten U, Goletz S. What makes cancer stem cell markers different? Springerplus. 2013; 2(1): 301[DOI][PubMed]
  • 56. Fatima S, Zhou S, Sorrentino BP. Abcg2 expression marks tissue-specific stem cells in multiple organs in a mouse progeny tracking model. Stem Cells. 2012; 30(2): 210-21[DOI][PubMed]
  • 57. Barker N, van Es JH, Kuipers J, Kujala P, van den Born M, Cozijnsen M, et al. Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature. 2007; 449(7165): 1003-7[DOI][PubMed]
  • 58. Douville J, Beaulieu R, Balicki D. ALDH1 as a functional marker of cancer stem and progenitor cells. Stem Cells Dev. 2009; 18(1): 17-25[DOI][PubMed]
  • 59. Medema JP. Cancer stem cells: the challenges ahead. Nat Cell Biol. 2013; 15(4): 338-44[DOI][PubMed]
  • 60. Madka V, Rao CV. Cancer stem cell markers as potential targets for epithelial cancers. Indian J Exp Biol. 2011; 49(11): 826-35[PubMed]
  • 61. Notarbartolo M, Poma P, Perri D, Dusonchet L, Cervello M, D'Alessandro N. Antitumor effects of curcumin, alone or in combination with cisplatin or doxorubicin, on human hepatic cancer cells. Analysis of their possible relationship to changes in NF-kB activation levels and in IAP gene expression. Cancer Lett. 2005; 224(1): 53-65[DOI][PubMed]
  • 62. Wilken R, Veena MS, Wang MB, Srivatsan ES. Curcumin: A review of anti-cancer properties and therapeutic activity in head and neck squamous cell carcinoma. Mol Cancer. 2011; 10: 12[DOI][PubMed]
  • 63. Johnson JJ, Mukhtar H. Curcumin for chemoprevention of colon cancer. Cancer Lett. 2007; 255(2): 170-81[DOI][PubMed]
  • 64. Chen HW, Lee JY, Huang JY, Wang CC, Chen WJ, Su SF, et al. Curcumin inhibits lung cancer cell invasion and metastasis through the tumor suppressor HLJ1. Cancer Res. 2008; 68(18): 7428-38[DOI][PubMed]
  • 65. Dorai T, Cao YC, Dorai B, Buttyan R, Katz AE. Therapeutic potential of curcumin in human prostate cancer. III. Curcumin inhibits proliferation, induces apoptosis, and inhibits angiogenesis of LNCaP prostate cancer cells in vivo. Prostate. 2001; 47(4): 293-303[DOI][PubMed]
  • 66. Shi M, Cai Q, Yao L, Mao Y, Ming Y, Ouyang G. Antiproliferation and apoptosis induced by curcumin in human ovarian cancer cells. Cell Biol Int. 2006; 30(3): 221-6[DOI][PubMed]
  • 67. Dhillon N, Aggarwal BB, Newman RA, Wolff RA, Kunnumakkara AB, Abbruzzese JL, et al. Phase II trial of curcumin in patients with advanced pancreatic cancer. Clin Cancer Res. 2008; 14(14): 4491-9[DOI][PubMed]
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