Journal of Human Genetics and Genomics

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The Most Well - known Markers of CSCs and Their Role in Growth of Tumors, Drug Resistance and Metastasis

Mohammad Javad Dehghan Esmatabadi 1 , * , Fatemeh Movahedi Motlagh 2 , 3 , Azadeh Etemadzadeh 4 and Samira Hajigholami 5
Authors Information
1 Malek - Ashtar University of Technology, Tehran, Iran
2 Cellular and Molecular Research Center, Faculty of Medicine, Sabzevar University of Medical Sciences, Sabzevar, Iran
3 Department of Medical Genetics, Tehran University of Medical Sciences, Tehran, Iran
4 Institute of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran
5 Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
Article information
  • Journal of Human Genetics and Genomics: July 2018, 2 (1); e65253
  • Published Online: July 27, 2017
  • Article Type: Review Article
  • Received: May 27, 2017
  • Revised: June 20, 2017
  • Accepted: July 25, 2017
  • DOI: 10.5812/jhgg.65253

How to Cite: Dehghan Esmatabadi M J, Movahedi Motlagh F, Etemadzadeh A, Hajigholami S. The Most Well - known Markers of CSCs and Their Role in Growth of Tumors, Drug Resistance and Metastasis, J Human Gen Genom. 2018 ; 2(1):e65253. doi: 10.5812/jhgg.65253.

Copyright © 2017, Journal of Human Genetics and Genomics. 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. Results
3. Conclusions
  • 1. Mansouri A, Abbaszadegan MR, Gholamin M. A Review on the Biology of Cancer Stem Cells. Stem Cell Discov. 2014;4(4):83-9. doi: 10.4236/scd.2014.44009.
  • 2. Ojha R, Bhattacharyya S, Singh SK. Autophagy in Cancer Stem Cells: A Potential Link Between Chemoresistance, Recurrence, and Metastasis. Biores Open Access. 2015;4(1):97-108. doi: 10.1089/biores.2014.0035. [PubMed: 26309786]. [PubMed Central: PMC4497670].
  • 3. Fanali C, Lucchetti D, Farina M, Corbi M, Cufino V, Cittadini A, et al. Cancer stem cells in colorectal cancer from pathogenesis to therapy: controversies and perspectives. World J Gastroenterol. 2014;20(4):923-42. doi: 10.3748/wjg.v20.i4.923. [PubMed: 24574766]. [PubMed Central: PMC3921545].
  • 4. Litvinov SV, Velders MP, Bakker HA, Fleuren GJ, Warnaar SO. Ep-CAM: a human epithelial antigen is a homophilic cell-cell adhesion molecule. J Cell Biol. 1994;125(2):437-46. [PubMed: 8163559]. [PubMed Central: PMC2120036].
  • 5. Munz M, Kieu C, Mack B, Schmitt B, Zeidler R, Gires O. The carcinoma-associated antigen EpCAM upregulates c-myc and induces cell proliferation. Oncogene. 2004;23(34):5748-58. doi: 10.1038/sj.onc.1207610. [PubMed: 15195135].
  • 6. Baeuerle PA, Gires O. EpCAM (CD326) finding its role in cancer. Br J Cancer. 2007;96(3):417-23. doi: 10.1038/sj.bjc.6603494. [PubMed: 17211480]. [PubMed Central: PMC2360029].
  • 7. Liu C, Kelnar K, Liu B, Chen X, Calhoun-Davis T, Li H, et al. The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44. Nat Med. 2011;17(2):211-5. doi: 10.1038/nm.2284. [PubMed: 21240262]. [PubMed Central: PMC3076220].
  • 8. Armstrong A, Eck SL. EpCAM: A New Therapeutic Target for an Old Cancer Antigen. Canc Biol Ther. 2014;2(4):320-5. doi: 10.4161/cbt.2.4.451.
  • 9. Tomita N, Yamano T, Matsubara N, Tamura K. [A novel genetic disorder of Lynch syndrome - EPCAM gene deletion]. Gan To Kagaku Ryoho. 2013;40(2):143-7. [PubMed: 23411950].
  • 10. Tabu K, Bizen N, Taga T, Tanaka S. Gene Regulation of Prominin-1 (CD133) in Normal and Cancerous Tissues. Adv Exp Med Biol. 2013;777:73-85. doi: 10.1007/978-1-4614-5894-4_5. [PubMed: 23161076].
  • 11. Yin AH, Miraglia S, Zanjani ED, Almeida-Porada G, Ogawa M, Leary AG, et al. AC133, a novel marker for human hematopoietic stem and progenitor cells. Blood. 1997;90(12):5002-12. [PubMed: 9389720].
  • 12. Zhou L, Wei X, Cheng L, Tian J, Jiang JJ. CD133, one of the markers of cancer stem cells in Hep-2 cell line. Laryngoscope. 2007;117(3):455-60. doi: 10.1097/01.mlg.0000251586.15299.35. [PubMed: 17334305].
  • 13. Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, et al. Identification of human brain tumour initiating cells. Nature. 2004;432(7015):396-401. doi: 10.1038/nature03128. [PubMed: 15549107].
  • 14. 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(9):4010-5. doi: 10.1158/0008-5472.CAN-06-4180. [PubMed: 17483311].
  • 15. Ogden AT, Waziri AE, Lochhead RA, Fusco D, Lopez K, Ellis JA, et al. Identification of A2B5+CD133- tumor-initiating cells in adult human gliomas. Neurosurgery. 2008;62(2):505-14. discussion 514-5. doi: 10.1227/01.neu.0000316019.28421.95. [PubMed: 18382330].
  • 16. Eramo A, Lotti F, Sette G, Pilozzi E, Biffoni M, Di Virgilio A, et al. Identification and expansion of the tumorigenic lung cancer stem cell population. Cell Death Differ. 2008;15(3):504-14. doi: 10.1038/sj.cdd.4402283. [PubMed: 18049477].
  • 17. Chiba T, Zheng YW, Kita K, Yokosuka O, Saisho H, Onodera M, et al. Enhanced self-renewal capability in hepatic stem/progenitor cells drives cancer initiation. Gastroenterology. 2007;133(3):937-50. doi: 10.1053/j.gastro.2007.06.016. [PubMed: 17673212].
  • 18. Matsui W, Huff CA, Wang Q, Malehorn MT, Barber J, Tanhehco Y, et al. Characterization of clonogenic multiple myeloma cells. Blood. 2004;103(6):2332-6. doi: 10.1182/blood-2003-09-3064. [PubMed: 14630803]. [PubMed Central: PMC3311914].
  • 19. Pearce DJ, Taussig D, Simpson C, Allen K, Rohatiner AZ, Lister TA, et al. Characterization of cells with a high aldehyde dehydrogenase activity from cord blood and acute myeloid leukemia samples. Stem Cells. 2005;23(6):752-60. doi: 10.1634/stemcells.2004-0292. [PubMed: 15917471].
  • 20. 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(5):555-67. doi: 10.1016/j.stem.2007.08.014. [PubMed: 18371393]. [PubMed Central: PMC2423808].
  • 21. Jiang F, Qiu Q, Khanna A, Todd NW, Deepak J, Xing L, et al. Aldehyde dehydrogenase 1 is a tumor stem cell-associated marker in lung cancer. Mol Cancer Res. 2009;7(3):330-8. doi: 10.1158/1541-7786.MCR-08-0393. [PubMed: 19276181]. [PubMed Central: PMC4255559].
  • 22. Chen YC, Chen YW, Hsu HS, Tseng LM, Huang PI, Lu KH, et al. Aldehyde dehydrogenase 1 is a putative marker for cancer stem cells in head and neck squamous cancer. Biochem Biophys Res Commun. 2009;385(3):307-13. doi: 10.1016/j.bbrc.2009.05.048. [PubMed: 19450560].
  • 23. Moreb J. Aldehyde Dehydrogenase as a Marker for Stem Cells. Curr Stem Cell Res Ther. 2008;3(4):237-46. doi: 10.2174/157488808786734006.
  • 24. Ades EW, Zwerner RK, Acton RT, Balch CM. Isolation and partial characterization of the human homologue of Thy-1. J Exp Med. 1980;151(2):400-6. [PubMed: 6153212]. [PubMed Central: PMC2185777].
  • 25. Rege TA, Hagood JS. Thy-1 as a regulator of cell-cell and cell-matrix interactions in axon regeneration, apoptosis, adhesion, migration, cancer, and fibrosis. FASEB J. 2006;20(8):1045-54. doi: 10.1096/fj.05-5460rev. [PubMed: 16770003].
  • 26. Buishand FO, Arkesteijn GJ, Feenstra LR, Oorsprong CW, Mestemaker M, Starke A, et al. Identification of CD90 as Putative Cancer Stem Cell Marker and Therapeutic Target in Insulinomas. Stem Cells Dev. 2016;25(11):826-35. doi: 10.1089/scd.2016.0032. [PubMed: 27049037]. [PubMed Central: PMC4892226].
  • 27. 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(2):153-66. doi: 10.1016/j.ccr.2008.01.013. [PubMed: 18242515].
  • 28. Yamazaki H, Nishida H, Iwata S, Dang NH, Morimoto C. CD90 and CD110 correlate with cancer stem cell potentials in human T-acute lymphoblastic leukemia cells. Biochem Biophys Res Commun. 2009;383(2):172-7. doi: 10.1016/j.bbrc.2009.03.127. [PubMed: 19341705].
  • 29. He J, Liu Y, Xie X, Zhu T, Soules M, DiMeco F, et al. Identification of cell surface glycoprotein markers for glioblastoma-derived stem-like cells using a lectin microarray and LC-MS/MS approach. J Proteome Res. 2010;9(5):2565-72. doi: 10.1021/pr100012p. [PubMed: 20235609]. [PubMed Central: PMC2866009].
  • 30. Lobba AR, Forni MF, Carreira AC, Sogayar MC. Differential expression of CD90 and CD14 stem cell markers in malignant breast cancer cell lines. Cytometry A. 2012;81(12):1084-91. doi: 10.1002/cyto.a.22220. [PubMed: 23090904].
  • 31. Abeysinghe HR, Li LQ, Guckert NL, Reeder J, Wang N. THY-1 induction is associated with up-regulation of fibronectin and thrombospondin-1 in human ovarian cancer. Cancer Genet Cytogenet. 2005;161(2):151-8. doi: 10.1016/j.cancergencyto.2005.02.014. [PubMed: 16102586].
  • 32. Rege TA, Hagood JS. Thy-1, a versatile modulator of signaling affecting cellular adhesion, proliferation, survival, and cytokine/growth factor responses. Biochim Biophys Acta. 2006;1763(10):991-9. doi: 10.1016/j.bbamcr.2006.08.008. [PubMed: 16996153]. [PubMed Central: PMC1781924].
  • 33. Yamashita T, Honda M, Nakamoto Y, Baba M, Nio K, Hara Y, et al. Discrete nature of EpCAM+ and CD90+ cancer stem cells in human hepatocellular carcinoma. Hepatology. 2013;57(4):1484-97. doi: 10.1002/hep.26168. [PubMed: 23174907].
  • 34. Spring FA, Dalchau R, Daniels GL, Mallinson G, Judson PA, Parsons SF, et al. The Ina and Inb blood group antigens are located on a glycoprotein of 80,000 MW (the CDw44 glycoprotein) whose expression is influenced by the In(Lu) gene. Immunology. 1988;64(1):37-43. [PubMed: 2454887]. [PubMed Central: PMC1385183].
  • 35. Louderbough JM, Schroeder JA. Understanding the dual nature of CD44 in breast cancer progression. Mol Cancer Res. 2011;9(12):1573-86. doi: 10.1158/1541-7786.MCR-11-0156. [PubMed: 21970856].
  • 36. Ponta H, Sherman L, Herrlich PA. CD44: from adhesion molecules to signalling regulators. Nat Rev Mol Cell Biol. 2003;4(1):33-45. doi: 10.1038/nrm1004. [PubMed: 12511867].
  • 37. Baaten BJ, Li CR, Bradley LM. Multifaceted regulation of T cells by CD44. Commun Integr Biol. 2010;3(6):508-12. doi: 10.4161/cib.3.6.13495. [PubMed: 21331226]. [PubMed Central: PMC3038050].
  • 38. Trapasso S, Allegra E. Role of CD44 as a marker of cancer stem cells in head and neck cancer. Biologics. 2012;6:379-83. doi: 10.2147/BTT.S37906. [PubMed: 23152667]. [PubMed Central: PMC3496191].
  • 39. 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 U S A. 2007;104(3):973-8. doi: 10.1073/pnas.0610117104. [PubMed: 17210912]. [PubMed Central: PMC1783424].
  • 40. Reiter RE, Gu Z, Watabe T, Thomas G, Szigeti K, Davis E, et al. Prostate stem cell antigen: A cell surface marker overexpressed in prostate cancer. Proc Natl Acad Sci Unit States Am. 1998;95(4):1735-40. doi: 10.1073/pnas.95.4.1735.
  • 41. Gu Z, Thomas G, Yamashiro J, Shintaku IP, Dorey F, Raitano A, et al. Prostate stem cell antigen (PSCA) expression increases with high gleason score, advanced stage and bone metastasis in prostate cancer. Oncogene. 2000;19(10):1288-96. doi: 10.1038/sj.onc.1203426.
  • 42. Argani P, Rosty C, Reiter RE, Wilentz RE, Murugesan SR, Leach SD, et al. Discovery of new markers of cancer through serial analysis of gene expression: prostate stem cell antigen is overexpressed in pancreatic adenocarcinoma. Cancer Res. 2001;61(11):4320-4. [PubMed: 11389052].
  • 43. Amara N, Palapattu GS, Schrage M, Gu Z, Thomas GV, Dorey F, et al. Prostate stem cell antigen is overexpressed in human transitional cell carcinoma. Cancer Res. 2001;61(12):4660-5. [PubMed: 11406532].
  • 44. Zhigang Z, Wenlv S. Prostate stem cell antigen (PSCA) expression in human prostate cancer tissues and its potential role in prostate carcinogenesis and progression of prostate cancer. World J Surg Oncol. 2004;2:13. doi: 10.1186/1477-7819-2-13. [PubMed: 15132743]. [PubMed Central: PMC420493].
  • 45. Wu X, Ye Y, Kiemeney LA, Sulem P, Rafnar T, Matullo G, et al. Genetic variation in the prostate stem cell antigen gene PSCA confers susceptibility to urinary bladder cancer. Nat Genet. 2009;41(9):991-5. doi: 10.1038/ng.421. [PubMed: 19648920]. [PubMed Central: PMC3313685].
  • 46. Douds JJ, Long DJ, Kim AS, Li S. Diagnostic and prognostic significance of CD200 expression and its stability in plasma cell myeloma. J Clin Pathol. 2014;67(9):792-6. doi: 10.1136/jclinpath-2014-202421. [PubMed: 24958785].
  • 47. Kawasaki BT, Mistree T, Hurt EM, Kalathur M, Farrar WL. Co-expression of the toleragenic glycoprotein, CD200, with markers for cancer stem cells. Biochem Biophys Res Commun. 2007;364(4):778-82. doi: 10.1016/j.bbrc.2007.10.067. [PubMed: 17964286]. [PubMed Central: PMC2168034].
  • 48. Petermann KB, Rozenberg GI, Zedek D, Groben P, McKinnon K, Buehler C, et al. CD200 is induced by ERK and is a potential therapeutic target in melanoma. J Clin Invest. 2007;117(12):3922-9. doi: 10.1172/JCI32163. [PubMed: 18008004]. [PubMed Central: PMC2075477].
  • 49. Rosenblum MD, Olasz E, Woodliff JE, Johnson BD, Konkol MC, Gerber KA, et al. CD200 is a novel p53-target gene involved in apoptosis-associated immune tolerance. Blood. 2004;103(7):2691-8. doi: 10.1182/blood-2003-09-3184. [PubMed: 14644999].
  • 50. Kraus S, Shapira S, Kazanov D, Naumov I, Moshkowitz M, Santo E, et al. Predictive Levels of CD24 in Peripheral Blood Leukocytes for the Early Detection of Colorectal Adenomas and Adenocarcinomas. Dis Markers. 2015;2015:916098. doi: 10.1155/2015/916098. [PubMed: 26078485]. [PubMed Central: PMC4442284].
  • 51. Jaggupilli A, Elkord E. Significance of CD44 and CD24 as cancer stem cell markers: an enduring ambiguity. Clin Dev Immunol. 2012;2012:708036. doi: 10.1155/2012/708036. [PubMed: 22693526]. [PubMed Central: PMC3369436].
  • 52. Li O, Zheng P, Liu Y. CD24 expression on T cells is required for optimal T cell proliferation in lymphopenic host. J Exp Med. 2004;200(8):1083-9. doi: 10.1084/jem.20040779. [PubMed: 15477346]. [PubMed Central: PMC2211842].
  • 53. Lim SC, Oh SH. The role of CD24 in various human epithelial neoplasias. Pathol Res Pract. 2005;201(7):479-86. doi: 10.1016/j.prp.2005.05.004. [PubMed: 16164042].
  • 54. Lee HJ, Choe G, Jheon S, Sung SW, Lee CT, Chung JH. CD24, a novel cancer biomarker, predicting disease-free survival of non-small cell lung carcinomas: a retrospective study of prognostic factor analysis from the viewpoint of forthcoming (seventh) new TNM classification. J Thorac Oncol. 2010;5(5):649-57. doi: 10.1097/JTO.0b013e3181d5e554. [PubMed: 20354454].
  • 55. Li C, Heidt DG, Dalerba P, Burant CF, Zhang L, Adsay V, et al. Identification of pancreatic cancer stem cells. Cancer Res. 2007;67(3):1030-7. doi: 10.1158/0008-5472.CAN-06-2030. [PubMed: 17283135].
  • 56. Biddle A, Gammon L, Fazil B, Mackenzie IC. CD44 staining of cancer stem-like cells is influenced by down-regulation of CD44 variant isoforms and up-regulation of the standard CD44 isoform in the population of cells that have undergone epithelial-to-mesenchymal transition. PLoS One. 2013;8(2). e57314. doi: 10.1371/journal.pone.0057314. [PubMed: 23437366]. [PubMed Central: PMC3577706].
  • 57. Chen W, Dong J, Haiech J, Kilhoffer MC, Zeniou M. Cancer Stem Cell Quiescence and Plasticity as Major Challenges in Cancer Therapy. Stem Cells Int. 2016;2016:1740936. doi: 10.1155/2016/1740936. [PubMed: 27418931]. [PubMed Central: PMC4932171].
  • 58. Keysar SB, Jimeno A. More than markers: biological significance of cancer stem cell-defining molecules. Mol Cancer Ther. 2010;9(9):2450-7. doi: 10.1158/1535-7163.MCT-10-0530. [PubMed: 20716638]. [PubMed Central: PMC3618879].
  • 59. Krause M, Dubrovska A, Linge A, Baumann M. Cancer stem cells: Radioresistance, prediction of radiotherapy outcome and specific targets for combined treatments. Adv Drug Deliv Rev. 2017;109:63-73. doi: 10.1016/j.addr.2016.02.002. [PubMed: 26877102].

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