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Lessons from common markers of tumor-initiating cells in solid cancers

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Abstract

Tumor-initiating cells (TICs) have emerged as the driving force of carcinomas, which appear as hierarchically structured. TICs as opposed to the tumor bulk display tumor forming potential, which is linked to a certain degree of self-renewal and differentiation, both major features of stem cells. Markers such as CD44, CD133, CD24, EpCAM, CD166, Lgr5, CD47, and ALDH have been described, which allow for the prospective enrichment of TICs. It is conspicuous that the same markers allow for an enrichment of TICs in various entities and, on the other hand, that different combinations of these markers were independently reported for the same tumor entity. Potential functions of these markers in the regulation of TIC phenotypes remained somewhat neglected although they might give insights in common molecular themes of TICs. The present review discusses major TIC markers with respect to their function and potential contributions to the tumorigenic phenotype of TICs.

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References

  1. Visvader JE, Lindeman GJ (2008) Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nat Rev Cancer 8(10):755–768

    Article  PubMed  CAS  Google Scholar 

  2. Quintana E, Shackleton M, Sabel MS, Fullen DR, Johnson TM, Morrison SJ (2008) Efficient tumour formation by single human melanoma cells. Nature 456(7222):593–598. doi:10.1038/nature07567

    Article  PubMed  CAS  Google Scholar 

  3. Kelly PN, Dakic A, Adams JM, Nutt SL, Strasser A (2007) Tumor growth need not be driven by rare cancer stem cells. Science 317(5836):337. doi:10.1126/science.1142596

    Article  PubMed  CAS  Google Scholar 

  4. Gupta PB, Chaffer CL, Weinberg RA (2009) Cancer stem cells: mirage or reality? Nat Med 15(9):1010–1012. doi:10.1038/nm0909-1010

    Article  PubMed  CAS  Google Scholar 

  5. Jaenisch R, Young R (2008) Stem cells, the molecular circuitry of pluripotency and nuclear reprogramming. Cell 132(4):567–582

    Article  PubMed  CAS  Google Scholar 

  6. Vermeulen L, De Sousa EMF, van der Heijden M, Cameron K, de Jong JH, Borovski T, Tuynman JB, Todaro M, Merz C, Rodermond H, Sprick MR, Kemper K, Richel DJ, Stassi G, Medema JP (2010) Wnt activity defines colon cancer stem cells and is regulated by the microenvironment. Nat Cell Biol 12(5):468–476. doi:10.1038/ncb2048

    Article  PubMed  CAS  Google Scholar 

  7. Wielenga VJ, Smits R, Korinek V, Smit L, Kielman M, Fodde R, Clevers H, Pals ST (1999) Expression of CD44 in Apc and Tcf mutant mice implies regulation by the WNT pathway. Am J Pathol 154(2):515–523. doi:10.1016/S0002-9440(10)65297-2

    Article  PubMed  CAS  Google Scholar 

  8. Dalerba P, Dylla SJ, Park IK, Liu R, Wang X, Cho RW, Hoey T, Gurney A, Huang EH, Simeone DM, Shelton AA, Parmiani G, Castelli C, Clarke MF (2007) Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci USA 104(24):10158–10163

    Article  PubMed  CAS  Google Scholar 

  9. Prince ME, Sivanandan R, Kaczorowski A, Wolf GT, Kaplan MJ, Dalerba P, Weissman IL, Clarke MF, Ailles LE (2007) Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proc Natl Acad Sci USA 104(3):973–978

    Article  PubMed  CAS  Google Scholar 

  10. Leung EL, Fiscus RR, Tung JW, Tin VP, Cheng LC, Sihoe AD, Fink LM, Ma Y, Wong MP (2010) Non-small cell lung cancer cells expressing CD44 are enriched for stem cell-like properties. PLoS One 5(11):e14062. doi:10.1371/journal.pone.0014062

    Article  PubMed  Google Scholar 

  11. Zhu Z, Hao X, Yan M, Yao M, Ge C, Gu J, Li J (2010) Cancer stem/progenitor cells are highly enriched in CD133+CD44+ population in hepatocellular carcinoma. Int J Cancer 126(9):2067–2078. doi:10.1002/ijc.24868

    PubMed  CAS  Google Scholar 

  12. Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF (2003) Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 100(7):3983–3988

    Article  PubMed  CAS  Google Scholar 

  13. Mack B, Gires O (2008) CD44s and CD44v6 expression in head and neck epithelia. PLoS ONE 3(10):e3360

    Article  PubMed  Google Scholar 

  14. Kawano T, Nakamura Y, Yanoma S, Kubota A, Furukawa M, Miyagi Y, Tsukuda M (2004) Expression of E-cadherin, and CD44s and CD44v6 and its association with prognosis in head and neck cancer. Auris Nasus Larynx 31(1):35–41

    Article  PubMed  Google Scholar 

  15. Lobo NA, Shimono Y, Qian D, Clarke MF (2007) The biology of cancer stem cells. Annu Rev Cell Dev Biol 23:675–699. doi:10.1146/annurev.cellbio.22.010305.104154

    Article  PubMed  CAS  Google Scholar 

  16. Zoller M (2011) CD44: can a cancer-initiating cell profit from an abundantly expressed molecule? Nat Rev Cancer 11(4):254–267. doi:10.1038/nrc3023

    Article  PubMed  Google Scholar 

  17. Ponta H, Sherman L, Herrlich PA (2003) CD44: from adhesion molecules to signalling regulators. Nat Rev Mol Cell Biol 4(1):33–45

    Article  PubMed  CAS  Google Scholar 

  18. Nagano O, Saya H (2004) Mechanism and biological significance of CD44 cleavage. Cancer Sci 95(12):930–935

    Article  PubMed  CAS  Google Scholar 

  19. Pelletier L, Guillaumot P, Freche B, Luquain C, Christiansen D, Brugiere S, Garin J, Manie SN (2006) Gamma-secretase-dependent proteolysis of CD44 promotes neoplastic transformation of rat fibroblastic cells. Cancer Res 66(7):3681–3687. doi:10.1158/0008-5472.CAN-05-3870

    Article  PubMed  CAS  Google Scholar 

  20. Jin L, Hope KJ, Zhai Q, Smadja-Joffe F, Dick JE (2006) Targeting of CD44 eradicates human acute myeloid leukemic stem cells. Nat Med 12(10):1167–1174. doi:10.1038/nm1483

    Article  PubMed  Google Scholar 

  21. Avigdor A, Goichberg P, Shivtiel S, Dar A, Peled A, Samira S, Kollet O, Hershkoviz R, Alon R, Hardan I, Ben-Hur H, Naor D, Nagler A, Lapidot T (2004) CD44 and hyaluronic acid cooperate with SDF-1 in the trafficking of human CD34+ stem/progenitor cells to bone marrow. Blood 103(8):2981–2989. doi:10.1182/blood-2003-10-3611

    Article  PubMed  CAS  Google Scholar 

  22. Zeilstra J, Joosten SP, Dokter M, Verwiel E, Spaargaren M, Pals ST (2008) Deletion of the WNT target and cancer stem cell marker CD44 in Apc(Min/+) mice attenuates intestinal tumorigenesis. Cancer Res 68(10):3655–3661. doi:10.1158/0008-5472.CAN-07-2940

    Article  PubMed  CAS  Google Scholar 

  23. Bourguignon LY, Xia W, Wong G (2009) Hyaluronan-mediated CD44 interaction with p300 and SIRT1 regulates beta-catenin signaling and NFkappaB-specific transcription activity leading to MDR1 and Bcl-xL gene expression and chemoresistance in breast tumor cells. J Biol Chem 284(5):2657–2671. doi:10.1074/jbc.M806708200

    Article  PubMed  CAS  Google Scholar 

  24. Bourguignon LY, Wong G, Earle C, Krueger K, Spevak CC (2010) Hyaluronan-CD44 interaction promotes c-Src-mediated twist signaling, MicroRNA-10b expression, and RhoA/RhoC up-regulation, leading to rho-kinase-associated cytoskeleton activation and breast tumor cell invasion. J Biol Chem 285(47):36721–36735. doi:10.1074/jbc.M110.162305

    Article  PubMed  CAS  Google Scholar 

  25. Li J, Zhou BP (2011) Activation of beta-catenin and Akt pathways by Twist are critical for the maintenance of EMT associated cancer stem cell-like characters. BMC Cancer 11:49. doi:10.1186/1471-2407-11-49

    Article  PubMed  Google Scholar 

  26. Corbeil D, Roper K, Fargeas CA, Joester A, Huttner WB (2001) Prominin: a story of cholesterol, plasma membrane protrusions and human pathology. Traffic 2(2):82–91

    Article  PubMed  CAS  Google Scholar 

  27. Yin AH, Miraglia S, Zanjani ED, Almeida-Porada G, Ogawa M, Leary AG, Olweus J, Kearney J, Buck DW (1997) AC133, a novel marker for human hematopoietic stem and progenitor cells. Blood 90(12):5002–5012

    PubMed  CAS  Google Scholar 

  28. Marzesco AM, Janich P, Wilsch-Brauninger M, Dubreuil V, Langenfeld K, Corbeil D, Huttner WB (2005) Release of extracellular membrane particles carrying the stem cell marker prominin-1 (CD133) from neural progenitors and other epithelial cells. J Cell Sci 118(Pt 13):2849–2858. doi:10.1242/jcs.02439

    Article  PubMed  CAS  Google Scholar 

  29. Uchida N, Buck DW, He D, Reitsma MJ, Masek M, Phan TV, Tsukamoto AS, Gage FH, Weissman IL (2000) Direct isolation of human central nervous system stem cells. Proc Natl Acad Sci USA 97(26):14720–14725. doi:10.1073/pnas.97.26.14720

    Article  PubMed  CAS  Google Scholar 

  30. Freund D, Bauer N, Boxberger S, Feldmann S, Streller U, Ehninger G, Werner C, Bornhauser M, Oswald J, Corbeil D (2006) Polarization of human hematopoietic progenitors during contact with multipotent mesenchymal stromal cells: effects on proliferation and clonogenicity. Stem Cells Dev 15(6):815–829. doi:10.1089/scd.2006.15.815

    Article  PubMed  CAS  Google Scholar 

  31. Horn PA, Tesch H, Staib P, Kube D, Diehl V, Voliotis D (1999) Expression of AC133, a novel hematopoietic precursor antigen, on acute myeloid leukemia cells. Blood 93(4):1435–1437

    PubMed  CAS  Google Scholar 

  32. Maw MA, Corbeil D, Koch J, Hellwig A, Wilson-Wheeler JC, Bridges RJ, Kumaramanickavel G, John S, Nancarrow D, Roper K, Weigmann A, Huttner WB, Denton MJ (2000) A frameshift mutation in prominin (mouse)-like 1 causes human retinal degeneration. Hum Mol Genet 9(1):27–34

    Article  PubMed  CAS  Google Scholar 

  33. O’Brien CA, Pollett A, Gallinger S, Dick JE (2007) A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 445(7123):106–110

    Article  PubMed  Google Scholar 

  34. Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C, De Maria R (2007) Identification and expansion of human colon-cancer-initiating cells. Nature 445(7123):111–115

    Article  PubMed  CAS  Google Scholar 

  35. Hermanek P, Hutter RV, Sobin LH, Wittekind C (1999) International Union Against Cancer. Classification of isolated tumor cells and micrometastasis. Cancer 86(12):2668–2673

    Article  PubMed  CAS  Google Scholar 

  36. Shi C, Tian R, Wang M, Wang X, Jiang J, Zhang Z, Li X, He Z, Gong W, Qin R CD44(+)CD133(+) population exhibits cancer stem cell-like characteristics in human gallbladder carcinoma. Cancer Biol Ther 10(11):1182–1190

  37. Curley MD, Therrien VA, Cummings CL, Sergent PA, Koulouris CR, Friel AM, Roberts DJ, Seiden MV, Scadden DT, Rueda BR, Foster R (2009) CD133 expression defines a tumor-initiating cell population in primary human ovarian cancer. Stem Cells 27(12):2875–2883. doi:10.1002/stem.236

    PubMed  CAS  Google Scholar 

  38. Bertolini G, Roz L, Perego P, Tortoreto M, Fontanella E, Gatti L, Pratesi G, Fabbri A, Andriani F, Tinelli S, Roz E, Caserini R, Lo Vullo S, Camerini T, Mariani L, Delia D, Calabro E, Pastorino U, Sozzi G (2009) Highly tumorigenic lung cancer CD133+ cells display stem-like features and are spared by cisplatin treatment. Proc Natl Acad Sci USA 106(38):16281–16286. doi:10.1073/pnas.0905653106

    Article  PubMed  CAS  Google Scholar 

  39. Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD, Dirks PB (2004) Identification of human brain tumour-initiating cells. Nature 432(7015):396–401

    Article  PubMed  CAS  Google Scholar 

  40. Al Dhaybi R, Sartelet H, Powell J, Kokta V (2010) Expression of CD133+ cancer stem cells in childhood malignant melanoma and its correlation with metastasis. Mod Pathol 23(3):376–380. doi: 10.1038/modpathol.2009.163

    Google Scholar 

  41. Suva ML, Riggi N, Stehle JC, Baumer K, Tercier S, Joseph JM, Suva D, Clement V, Provero P, Cironi L, Osterheld MC, Guillou L, Stamenkovic I (2009) Identification of cancer stem cells in Ewing’s sarcoma. Cancer Res 69(5):1776–1781. doi:10.1158/0008-5472.CAN-08-2242

    Article  PubMed  CAS  Google Scholar 

  42. Shmelkov SV, Butler JM, Hooper AT, Hormigo A, Kushner J, Milde T, St Clair R, Baljevic M, White I, Jin DK, Chadburn A, Murphy AJ, Valenzuela DM, Gale NW, Thurston G, Yancopoulos GD, D’Angelica M, Kemeny N, Lyden D, Rafii S (2008) CD133 expression is not restricted to stem cells, and both CD133 and CD133 metastatic colon cancer cells initiate tumors. J Clin Invest 118(6):2111–2120

    PubMed  CAS  Google Scholar 

  43. Navarro-Alvarez N, Kondo E, Kawamoto H, Hassan W, Yuasa T, Kubota Y, Seita M, Nakahara H, Hayashi T, Nishikawa Y, Hassan RA, Javed SM, Noguchi H, Matsumoto S, Nakaji S, Tanaka N, Kobayashi N, Soto-Gutierrez A (2010) Isolation and propagation of a human CD133(-) colon tumor-derived cell line with tumorigenic and angiogenic properties. Cell Transpl 19(6):865–877. doi:ct2259navarroalvarez[pii]10.3727/096368910X508997

    Article  Google Scholar 

  44. Beier CP, Beier D (2011) CD133-negative cancer stem cells in glioblastoma. Front Biosci (Elite Ed) 3:701–710

    Article  Google Scholar 

  45. Kemper K, Sprick MR, de Bree M, Scopelliti A, Vermeulen L, Hoek M, Zeilstra J, Pals ST, Mehmet H, Stassi G, Medema JP (2010) The AC133 epitope, but not the CD133 protein, is lost upon cancer stem cell differentiation. Cancer Res 70(2):719–729. doi:10.1158/0008-5472.CAN-09-1820

    Article  PubMed  CAS  Google Scholar 

  46. Griguer CE, Oliva CR, Gobin E, Marcorelles P, Benos DJ, Lancaster JR Jr, Gillespie GY (2008) CD133 is a marker of bioenergetic stress in human glioma. PLoS One 3(11):e3655. doi:10.1371/journal.pone.0003655

    Article  PubMed  Google Scholar 

  47. Fargeas CA, Huttner WB, Corbeil D (2007) Nomenclature of prominin-1 (CD133) splice variants—an update. Tissue Antigens 69(6):602–606. doi:10.1111/j.1399-0039.2007.00825.x

    Article  PubMed  CAS  Google Scholar 

  48. Bauer N, Fonseca AV, Florek M, Freund D, Jaszai J, Bornhauser M, Fargeas CA, Corbeil D (2008) New insights into the cell biology of hematopoietic progenitors by studying prominin-1 (CD133). Cells Tissues Organs 188(1–2):127–138

    Article  PubMed  CAS  Google Scholar 

  49. Hermann PC, Huber SL, Herrler T, Aicher A, Ellwart JW, Guba M, Bruns CJ, Heeschen C (2007) Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell 1(3):313–323

    Article  PubMed  CAS  Google Scholar 

  50. Horst D, Scheel SK, Liebmann S, Neumann J, Maatz S, Kirchner T, Jung A (2009) The cancer stem cell marker CD133 has high prognostic impact but unknown functional relevance for the metastasis of human colon cancer. J Pathol 219(4):427–434. doi:10.1002/path.2597

    Article  PubMed  CAS  Google Scholar 

  51. Zhu L, Gibson P, Currle DS, Tong Y, Richardson RJ, Bayazitov IT, Poppleton H, Zakharenko S, Ellison DW, Gilbertson RJ (2009) Prominin 1 marks intestinal stem cells that are susceptible to neoplastic transformation. Nature 457(7229):603–607. doi:10.1038/nature07589

    Article  PubMed  CAS  Google Scholar 

  52. Li C, Heidt DG, Dalerba P, Burant CF, Zhang L, Adsay V, Wicha M, Clarke MF, Simeone DM (2007) Identification of pancreatic cancer stem cells. Cancer Res 67(3):1030–1037

    Article  PubMed  CAS  Google Scholar 

  53. Munz M, Kieu C, Mack B, Schmitt B, Zeidler R, Gires O (2004) The carcinoma-associated antigen EpCAM upregulates c-myc and induces cell proliferation. Oncogene 23(34):5748–5758

    Article  PubMed  Google Scholar 

  54. Osta WA, Chen Y, Mikhitarian K, Mitas M, Salem M, Hannun YA, Cole DJ, Gillanders WE (2004) EpCAM is overexpressed in breast cancer and is a potential target for breast cancer gene therapy. Cancer Res 64(16):5818–5824

    Article  PubMed  CAS  Google Scholar 

  55. Nagao K, Zhu J, Heneghan MB, Hanson JC, Morasso MI, Tessarollo L, Mackem S, Udey MC (2009) Abnormal placental development and early embryonic lethality in EpCAM-null mice. PLoS One 4(12):e8543. doi:10.1371/journal.pone.0008543

    Article  PubMed  Google Scholar 

  56. Maetzel D, Denzel S, Mack B, Canis M, Went P, Benk M, Kieu C, Papior P, Baeuerle PA, Munz M, Gires O (2009) Nuclear signalling by tumour-associated antigen EpCAM. Nat Cell Biol 11(2):162–171. doi:10.1038/ncb1824

    Article  PubMed  CAS  Google Scholar 

  57. Johannessen M, Moller S, Hansen T, Moens U, Mc-rp-p VanGhelue (2006) The multifunctional roles of the four-and-a-half-LIM only protein FHL2. Cell Mol Life Sci 63(3):268–284

    Article  PubMed  CAS  Google Scholar 

  58. Li M, Wang J, Ng SS, Chan CY, Chen AC, Xia HP, Yew DT, Wong BC, Chen Z, Kung HF, Lin MC (2008) The four-and-a-half-LIM protein 2 (FHL2) is overexpressed in gliomas and associated with oncogenic activities. Glia 56(12):1328–1338

    Article  PubMed  Google Scholar 

  59. Wang J, Yang Y, Xia HH, Gu Q, Lin MC, Jiang B, Peng Y, Li G, An X, Zhang Y, Zhuang Z, Zhang Z, Kung HF, Wong BC (2007) Suppression of FHL2 expression induces cell differentiation and inhibits gastric and colon carcinogenesis. Gastroenterology 132(3):1066–1076

    Article  PubMed  CAS  Google Scholar 

  60. Kenny PA (2007) TACE: a new target in epidermal growth factor receptor dependent tumors. Differentiation 75(9):800–808

    Article  PubMed  CAS  Google Scholar 

  61. Selkoe DJ, Wolfe MS (2007) Presenilin: running with scissors in the membrane. Cell 131(2):215–221

    Article  PubMed  CAS  Google Scholar 

  62. Merchant NB, Voskresensky I, Rogers CM, Lafleur B, Dempsey PJ, Graves-Deal R, Revetta F, Foutch AC, Rothenberg ML, Washington MK, Coffey RJ (2008) TACE/ADAM-17: a component of the epidermal growth factor receptor axis and a promising therapeutic target in colorectal cancer. Clin Cancer Res 14(4):1182–1191

    Article  PubMed  CAS  Google Scholar 

  63. Reya T, Clevers H (2005) Wnt signalling in stem cells and cancer. Nature 434(7035):843–850

    Article  PubMed  CAS  Google Scholar 

  64. Reya T, Duncan AW, Ailles L, Domen J, Scherer DC, Willert K, Hintz L, Nusse R, Weissman IL (2003) A role for Wnt signalling in self-renewal of haematopoietic stem cells. Nature 423(6938):409–414

    Article  PubMed  CAS  Google Scholar 

  65. Yamashita T, Budhu A, Forgues M, Wang XW (2007) Activation of hepatic stem cell marker EpCAM by Wnt-beta-catenin signaling in hepatocellular carcinoma. Cancer Res 67(22):10831–10839

    Article  PubMed  CAS  Google Scholar 

  66. He TC, Sparks AB, Rago C, Hermeking H, Zawel L, da Costa LT, Morin PJ, Vogelstein B, Kinzler KW (1998) Identification of c-MYC as a target of the APC pathway. Science 281(5382):1509–1512

    Article  PubMed  CAS  Google Scholar 

  67. Wong DJ, Liu H, Ridky TW, Cassarino D, Segal E, Chang HY (2008) Module map of stem cell genes guides creation of epithelial cancer stem cells. Cell Stem Cell 2(4):333–344. doi:10.1016/j.stem.2008.02.009

    Article  PubMed  CAS  Google Scholar 

  68. Gonzalez B, Denzel S, Mack B, Conrad M, Gires O (2009) EpCAM is involved in maintenance of the murine embryonic stem cell phenotype. Stem Cells 27(8):1782–1791. doi:10.1002/stem.97

    Article  PubMed  CAS  Google Scholar 

  69. Ng VY, Ang SN, Chan JX, Choo AB (2009) Characterization of epithelial cell adhesion molecule as a surface marker on undifferentiated human embryonic stem cells. Stem Cells. doi:10.1002/stem.221

  70. Lu TY, Lu RM, Liao MY, Yu J, Chung CH, Kao CF, Wu HC (2010) Epithelial cell adhesion molecule regulation is associated with the maintenance of the undifferentiated phenotype of human embryonic stem cells. J Biol Chem 285(12):8719–8732. doi:10.1074/jbc.M109.077081

    Article  PubMed  CAS  Google Scholar 

  71. Munz M, Baeuerle PA, Gires O (2009) The emerging role of EpCAM in cancer and stem cell signaling. Cancer Res 69(14):5627–5629. doi:10.1158/0008-5472.CAN-09-0654

    Article  PubMed  CAS  Google Scholar 

  72. Denzel S, Maetzel D, Mack B, Eggert C, Barr G, Gires O (2009) Initial activation of EpCAM cleavage via cell-to-cell contact. BMC Cancer 9:402. doi:10.1186/1471-2407-9-402

    Article  PubMed  Google Scholar 

  73. Mukherjee S, Richardson AM, Rodriguez-Canales J, Ylaya K, Erickson HS, Player A, Kawasaki ES, Pinto PA, Choyke PL, Merino MJ, Albert PS, Chuaqui RF, Emmert-Buck MR (2009) Identification of EpCAM as a molecular target of prostate cancer stroma. Am J Pathol 175(6):2277–2287. doi:10.2353/ajpath.2009.090013

    Article  PubMed  CAS  Google Scholar 

  74. Chen HF, Chuang CY, Lee WC, Huang HP, Wu HC, Ho HN, Chen YJ, Kuo HC (2011) Surface marker epithelial cell adhesion molecule and E-cadherin facilitate the identification and selection of induced pluripotent stem cells. Stem Cell Rev. doi:10.1007/s12015-011-9233-y

  75. Kay R, Rosten PM, Humphries RK (1991) CD24, a signal transducer modulating B cell activation responses, is a very short peptide with a glycosyl phosphatidylinositol membrane anchor. J Immunol 147(4):1412–1416

    PubMed  CAS  Google Scholar 

  76. Liu Y, Zheng P (2007) CD24: a genetic checkpoint in T cell homeostasis and autoimmune diseases. Trends Immunol 28(7):315–320. doi:10.1016/j.it.2007.05.001

    Article  PubMed  Google Scholar 

  77. Morel AP, Lievre M, Thomas C, Hinkal G, Ansieau S, Puisieux A (2008) Generation of breast cancer stem cells through epithelial-mesenchymal transition. PLoS One 3(8):e2888. doi:10.1371/journal.pone.0002888

    Article  PubMed  Google Scholar 

  78. Baumann P, Cremers N, Kroese F, Orend G, Chiquet-Ehrismann R, Uede T, Yagita H, Sleeman JP (2005) CD24 expression causes the acquisition of multiple cellular properties associated with tumor growth and metastasis. Cancer Res 65(23):10783–10793. doi:10.1158/0008-5472.CAN-05-0619

    Article  PubMed  CAS  Google Scholar 

  79. Ohneda O, Ohneda K, Arai F, Lee J, Miyamoto T, Fukushima Y, Dowbenko D, Lasky LA, Suda T (2001) ALCAM (CD166): its role in hematopoietic and endothelial development. Blood 98(7):2134–2142

    Article  PubMed  CAS  Google Scholar 

  80. Swart GW (2002) Activated leukocyte cell adhesion molecule (CD166/ALCAM): developmental and mechanistic aspects of cell clustering and cell migration. Eur J Cell Biol 81(6):313–321

    Article  PubMed  CAS  Google Scholar 

  81. Weidle UH, Eggle D, Klostermann S, Swart GW (2010) ALCAM/CD166: cancer-related issues. Cancer Genomics Proteomics 7(5):231–243

    PubMed  CAS  Google Scholar 

  82. Rosso O, Piazza T, Bongarzone I, Rossello A, Mezzanzanica D, Canevari S, Orengo AM, Puppo A, Ferrini S, Fabbi M (2007) The ALCAM shedding by the metalloprotease ADAM17/TACE is involved in motility of ovarian carcinoma cells. Mol Cancer Res 5(12):1246–1253. doi:10.1158/1541-7786.MCR-07-0060

    Article  PubMed  CAS  Google Scholar 

  83. Jezierska A, Matysiak W, Motyl T (2006) ALCAM/CD166 protects breast cancer cells against apoptosis and autophagy. Med Sci Monit 12(8):BR263–BR273

    PubMed  CAS  Google Scholar 

  84. Van der Flier LG, Sabates-Bellver J, Oving I, Haegebarth A, De Palo M, Anti M, Van Gijn ME, Suijkerbuijk S, Van de Wetering M, Marra G, Clevers H (2007) The intestinal Wnt/TCF signature. Gastroenterology 132(2):628–632. doi:10.1053/j.gastro.2006.08.039

    Article  PubMed  Google Scholar 

  85. Haegebarth A, Clevers H (2009) Wnt signaling, lgr5, and stem cells in the intestine and skin. Am J Pathol 174(3):715–721. doi:10.2353/ajpath.2009.080758

    Article  PubMed  CAS  Google Scholar 

  86. Barker N, Ridgway RA, van Es JH, van de Wetering M, Begthel H, van den Born M, Danenberg E, Clarke AR, Sansom OJ, Clevers H (2009) Crypt stem cells as the cells-of-origin of intestinal cancer. Nature 457(7229):608–611. doi:10.1038/nature07602

    Article  PubMed  CAS  Google Scholar 

  87. Sato T, Vries RG, Snippert HJ, van de Wetering M, Barker N, Stange DE, van Es JH, Abo A, Kujala P, Peters PJ, Clevers H (2009) Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature 459(7244):262–265. doi:10.1038/nature07935

    Article  PubMed  CAS  Google Scholar 

  88. Lindberg FP, Gresham HD, Schwarz E, Brown EJ (1993) Molecular cloning of integrin-associated protein: an immunoglobulin family member with multiple membrane-spanning domains implicated in alpha v beta 3-dependent ligand binding. J Cell Biol 123(2):485–496

    Article  PubMed  CAS  Google Scholar 

  89. Gao AG, Frazier WA (1994) Identification of a receptor candidate for the carboxyl-terminal cell binding domain of thrombospondins. J Biol Chem 269(47):29650–29657

    PubMed  CAS  Google Scholar 

  90. Wang XQ, Frazier WA (1998) The thrombospondin receptor CD47 (IAP) modulates and associates with alpha2 beta1 integrin in vascular smooth muscle cells. Mol Biol Cell 9(4):865–874

    PubMed  CAS  Google Scholar 

  91. Chan KS, Espinosa I, Chao M, Wong D, Ailles L, Diehn M, Gill H, Presti J Jr, Chang HY, van de Rijn M, Shortliffe L, Weissman IL (2009) Identification, molecular characterization, clinical prognosis, and therapeutic targeting of human bladder tumor-initiating cells. Proc Natl Acad Sci USA 106(33):14016–14021. doi:10.1073/pnas.0906549106

    Article  PubMed  CAS  Google Scholar 

  92. Sick E, Boukhari A, Deramaudt T, Ronde P, Bucher B, Andre P, Gies JP, Takeda K (2011) Activation of CD47 receptors causes proliferation of human astrocytoma but not normal astrocytes via an Akt-dependent pathway. Glia 59(2):308–319. doi:10.1002/glia.21102

    Article  PubMed  Google Scholar 

  93. Majeti R, Chao MP, Alizadeh AA, Pang WW, Jaiswal S, Gibbs KD Jr, van Rooijen N, Weissman IL (2009) CD47 is an adverse prognostic factor and therapeutic antibody target on human acute myeloid leukemia stem cells. Cell 138(2):286–299. doi:10.1016/j.cell.2009.05.045

    Article  PubMed  CAS  Google Scholar 

  94. Chao MP, Alizadeh AA, Tang C, Myklebust JH, Varghese B, Gill S, Jan M, Cha AC, Chan CK, Tan BT, Park CY, Zhao F, Kohrt HE, Malumbres R, Briones J, Gascoyne RD, Lossos IS, Levy R, Weissman IL, Majeti R (2010) Anti-CD47 antibody synergizes with rituximab to promote phagocytosis and eradicate non-Hodgkin lymphoma. Cell 142(5):699–713. doi:10.1016/j.cell.2010.07.044

    Article  PubMed  CAS  Google Scholar 

  95. Ma I, Allan AL (2010) The role of human aldehyde dehydrogenase in normal and cancer stem cells. Stem Cell Rev. doi:10.1007/s12015-010-9208-4

  96. Gudas LJ, Wagner JA (2011) Retinoids regulate stem cell differentiation. J Cell Physiol 226(2):322–330. doi:10.1002/jcp.22417

    Article  PubMed  CAS  Google Scholar 

  97. Zhang M, Shoeb M, Goswamy J, Liu P, Xiao TL, Hogan D, Campbell GA, Ansari NH (2010) Overexpression of aldehyde dehydrogenase 1A1 reduces oxidation-induced toxicity in SH-SY5Y neuroblastoma cells. J Neurosci Res 88(3):686–694. doi:10.1002/jnr.22230

    PubMed  CAS  Google Scholar 

  98. Tanei T, Morimoto K, Shimazu K, Kim SJ, Tanji Y, Taguchi T, Tamaki Y, Noguchi S (2009) Association of breast cancer stem cells identified by aldehyde dehydrogenase 1 expression with resistance to sequential Paclitaxel and epirubicin-based chemotherapy for breast cancers. Clin Cancer Res 15(12):4234–4241. doi:10.1158/1078-0432.CCR-08-1479

    Article  PubMed  CAS  Google Scholar 

  99. Carpentino JE, Hynes MJ, Appelman HD, Zheng T, Steindler DA, Scott EW, Huang EH (2009) Aldehyde dehydrogenase-expressing colon stem cells contribute to tumorigenesis in the transition from colitis to cancer. Cancer Res 69(20):8208–8215. doi:10.1158/0008-5472.CAN-09-1132

    Article  PubMed  CAS  Google Scholar 

  100. Bourguignon LY, Spevak CC, Wong G, Xia W, Gilad E (2009) Hyaluronan-CD44 interaction with protein kinase C(epsilon) promotes oncogenic signaling by the stem cell marker Nanog and the Production of microRNA-21, leading to down-regulation of the tumor suppressor protein PDCD4, anti-apoptosis, and chemotherapy resistance in breast tumor cells. J Biol Chem 284(39):26533–26546. doi:10.1074/jbc.M109.027466

    Article  PubMed  CAS  Google Scholar 

  101. Maaser K, Borlak J (2008) A genome-wide expression analysis identifies a network of EpCAM-induced cell cycle regulators. Br J Cancer 99(10):1635–1643

    Article  PubMed  CAS  Google Scholar 

  102. Litvinov SV, Balzar M, Winter MJ, Bakker HA, Briaire-de Bruijn IH, Prins F, Fleuren GJ, Warnaar SO (1997) Epithelial cell adhesion molecule (Ep-CAM) modulates cell-cell interactions mediated by classic cadherins. J Cell Biol 139(5):1337–1348

    Article  PubMed  CAS  Google Scholar 

  103. Gunthert U, Hofmann M, Rudy W, Reber S, Zoller M, Haussmann I, Matzku S, Wenzel A, Ponta H, Herrlich P (1991) A new variant of glycoprotein CD44 confers metastatic potential to rat carcinoma cells. Cell 65(1):13–24

    Article  PubMed  CAS  Google Scholar 

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OG is a consultant for Micromet Inc.

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  1. Department of Otorhinolaryngology, Head and Neck Surgery, Grosshadern Medical Center, Ludwig-Maximilians-University of Munich, Marchioninistr. 15, 81377, Munich, Germany

    Olivier Gires

  2. Clinical Cooperation Group Molecular Oncology, Helmholtz-Zentrum München, German Research Center for Environmental Health, and Head and Neck Research Department, Ludwig-Maximilians-University of Munich, Munich, Germany

    Olivier Gires

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Gires, O. Lessons from common markers of tumor-initiating cells in solid cancers. Cell. Mol. Life Sci. 68, 4009–4022 (2011). https://doi.org/10.1007/s00018-011-0772-9

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  • DOI: https://doi.org/10.1007/s00018-011-0772-9

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