title: Cancer stem cells in solid tumors: elusive or illusive?
abstract: During the past years in vivo transplantation experiments and in vitro colony-forming assays indicated that tumors arise only from rare cells. These cells were shown to bear self-renewal capacities and the ability to recapitulate all cell types within an individual tumor. Due to their phenotypic resemblance to normal stem cells, the term "cancer stem cells" is used. However, some pieces of the puzzle are missing: (a) a stringent definition of cancer stem cells in solid tumors (b) specific markers that only target cells that meet the criteria for a cancer stem cell in a certain type of tumor. These missing parts started an ongoing debate about which is the best method to identify and characterize cancer stem cells, or even if their mere existence is just an artifact caused by the experimental procedures. Recent findings query the cancer stem cell hypothesis for solid tumors itself since it was shown in xenograft transplantation experiments that under appropriate conditions tumor-initiating cells are not rare.In this review we critically discuss the challenges and prospects of the currently used major methods to identify cancer stem cells. Further on, we reflect the present discussion about the existence of cancer stem cells in solid tumors as well as the amount and characteristics of tumor-initiating cells and finally provide new perspectives like the correlation of cancer stem cells and induced pluripotent cells.
authors.affiliation: Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Ihnestrasse 63-73, 14195 Berlin, Germany. regenbre@molgen.mpg.de.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Welte
authors.forename: James
authors.initials: J
authors.lastname: Adjaye
authors.forename: Hans R
authors.initials: HR
authors.lastname: Lehrach
authors.forename: Christian Ra
authors.initials: CR
authors.lastname: Regenbrecht
references.citation: Front Biosci. 2006 Jan 01;11:733-42
references.pmid: 16146765
references.citation: PLoS One. 2008;3(10):e3469
references.pmid: 18941626
references.citation: Blood. 2002 Jan 15;99(2):507-12
references.pmid: 11781231
references.citation: Proc Natl Acad Sci U S A. 2006 Jul 25;103(30):11154-9
references.pmid: 16849428
references.citation: Proc Natl Acad Sci U S A. 2002 Sep 17;99(19):12339-44
references.pmid: 12218177
references.citation: J Int Med Res. 2009 Mar-Apr;37(2):503-10
references.pmid: 19383245
references.citation: Eur J Cancer. 2007 Mar;43(5):935-46
references.pmid: 17320377
references.citation: Cancer Res. 2007 Apr 15;67(8):3691-7
references.pmid: 17440081
references.citation: Nature. 2008 Dec 4;456(7222):593-8
references.pmid: 19052619
references.citation: Nat Biotechnol. 2008 Aug;26(8):916-24
references.pmid: 18594521
references.citation: Cancer Res. 2006 Feb 15;66(4):1891-5; discussion 1890
references.pmid: 16488984
references.citation: Br J Cancer. 2003 Oct 20;89(8):1581-9
references.pmid: 14562035
references.citation: Science. 1977 Jul 29;197(4302):461-3
references.pmid: 560061
references.citation: Pharmazie. 2009 May;64(5):296-300
references.pmid: 19530439
references.citation: Exp Hematol. 2002 Nov;30(11):1339-45
references.pmid: 12423688
references.citation: J Pathol. 2008 Apr;214(5):564-73
references.pmid: 18266310
references.citation: Cell. 1994 May 20;77(4):491-502
references.pmid: 7910522
references.citation: Cancer Res. 2007 Jun 15;67(12):5727-36
references.pmid: 17575139
references.citation: J Invest Dermatol. 2006 Jan;126(1):142-53
references.pmid: 16417230
references.citation: Nature. 2001 May 17;411(6835):349-54
references.pmid: 11357142
references.citation: J Biol Chem. 2000 Feb 25;275(8):5512-20
references.pmid: 10681530
references.citation: Nat Med. 2001 Sep;7(9):1028-34
references.pmid: 11533706
references.citation: Cell. 2006 Aug 25;126(4):663-76
references.pmid: 16904174
references.citation: Cell Tissue Res. 2005 Jan;319(1):15-26
references.pmid: 15558321
references.citation: Gastroenterology. 2005 Nov;129(5):1567-80
references.pmid: 16285956
references.citation: Nat Cell Biol. 2001 Sep;3(9):778-84
references.pmid: 11533656
references.citation: Cancer Sci. 2009 Jun;100(6):1040-6
references.pmid: 19385971
references.citation: Mod Pathol. 2007 Jan;20(1):102-7
references.pmid: 17143262
references.citation: J Clin Invest. 2000 Jul;106(1):3-8
references.pmid: 10880041
references.citation: Proc Natl Acad Sci U S A. 2009 Sep 22;106(38):16281-6
references.pmid: 19805294
references.citation: Nature. 2007 Jan 4;445(7123):111-5
references.pmid: 17122771
references.citation: Nat Med. 2009 Sep;15(9):1010-2
references.pmid: 19734877
references.citation: Br J Haematol. 2001 Oct;115(1):186-94
references.pmid: 11722432
references.citation: Science. 1992 Mar 27;255(5052):1707-10
references.pmid: 1553558
references.citation: Stem Cell Rev. 2008 Dec;4(4):319-28
references.pmid: 18561035
references.citation: Br J Cancer. 1973 Aug;28(2):123-35
references.pmid: 4730176
references.citation: Invest Ophthalmol Vis Sci. 2003 Jun;44(6):2764-73
references.pmid: 12766085
references.citation: Science. 2007 Jul 20;317(5836):337
references.pmid: 17641192
references.citation: Cancer Res. 2005 Jul 15;65(14):6207-19
references.pmid: 16024622
references.citation: Cell. 1991 Jul 12;66(1):85-94
references.pmid: 1712673
references.citation: Cell. 1998 Nov 25;95(5):605-14
references.pmid: 9845363
references.citation: J Photochem Photobiol B. 2003 May-Jun;70(2):107-15
references.pmid: 12849701
references.citation: Ann N Y Acad Sci. 2009 Sep;1176:154-69
references.pmid: 19796244
references.citation: Nature. 2004 Nov 18;432(7015):396-401
references.pmid: 15549107
references.citation: Proc Natl Acad Sci U S A. 2009 Jun 2;106(22):8912-7
references.pmid: 19447925
references.citation: Nature. 2003 May 15;423(6937):255-60
references.pmid: 12714970
references.citation: J Exp Med. 1996 Apr 1;183(4):1797-806
references.pmid: 8666936
references.citation: Exp Cell Res. 2006 Nov 15;312(19):3701-10
references.pmid: 17046749
references.citation: FEBS Lett. 2007 Apr 3;581(7):1435-40
references.pmid: 17362939
references.citation: Endocrinology. 2007 Apr;148(4):1797-803
references.pmid: 17234707
references.citation: Cancer Res. 1986 Jul;46(7):3556-9
references.pmid: 3708586
references.citation: Nature. 2008 Jan 17;451(7176):345-9
references.pmid: 18202660
references.citation: Cancer Res. 2008 Oct 1;68(19):7882-6
references.pmid: 18829544
references.citation: Clin Chim Acta. 2004 May;343(1-2):173-8
references.pmid: 15115691
references.citation: Cell Biol Int. 2009 Aug;33(8):807-15
references.pmid: 19477285
references.citation: Histopathology. 2009 Sep;55(3):284-93
references.pmid: 19723143
references.citation: Cancer Cell. 2005 Jan;7(1):17-23
references.pmid: 15652746
references.citation: Endocrinology. 2008 Mar;149(3):1314-22
references.pmid: 18063677
references.citation: Nat Genet. 1998 Aug;19(4):379-83
references.pmid: 9697701
references.citation: Cancer Res. 2005 Oct 15;65(20):9328-37
references.pmid: 16230395
references.citation: Semin Cancer Biol. 2005 Oct;15(5):378-86
references.pmid: 15975825
references.citation: Acta Unio Int Contra Cancrum. 1959;15(Suppl 1):196-8
references.pmid: 14420161
references.citation: Neoplasma. 2009;56(5):371-8
references.pmid: 19580337
references.citation: J Natl Cancer Inst. 1971 Feb;46(2):411-22
references.pmid: 5115909
references.citation: Methods Mol Biol. 2009;568:139-49
references.pmid: 19582424
references.citation: Stem Cells. 2006 Mar;24(3):506-13
references.pmid: 16239320
references.citation: J Clin Invest. 1977 Oct;60(4):846-54
references.pmid: 302265
references.citation: Proc Natl Acad Sci U S A. 2004 Sep 28;101(39):14228-33
references.pmid: 15381773
references.citation: Nat Biotechnol. 2008 Jul;26(7):795-7
references.pmid: 18568017
references.citation: Hepatology. 2006 Jul;44(1):240-51
references.pmid: 16799977
references.citation: Cancer Lett. 2010 May 28;291(2):150-7
references.pmid: 19913993
references.citation: Ann Surg Oncol. 2008 Feb;15(2):638-48
references.pmid: 17932721
references.citation: Proc Natl Acad Sci U S A. 2004 Jan 20;101(3):781-6
references.pmid: 14711994
references.citation: Nature. 2001 Nov 1;414(6859):105-11
references.pmid: 11689955
references.citation: Cancer Res. 2007 Apr 15;67(8):3716-24
references.pmid: 17440084
references.citation: Cancer Lett. 2008 Sep 8;268(1):1-9
references.pmid: 18487012
references.citation: Int J Clin Pract. 2008 Aug;62(8):1212-8
references.pmid: 18479363
references.citation: In Vitro Cell Dev Biol Anim. 2008 Jul-Aug;44(7):280-9
references.pmid: 18594936
references.citation: Int J Cancer. 2008 Feb 15;122(4):761-8
references.pmid: 17955491
references.citation: Cell Cycle. 2005 Feb;4(2):203-5
references.pmid: 15655356
references.citation: Nature. 2005 Apr 14;434(7035):843-50
references.pmid: 15829953
references.citation: Clin Transl Oncol. 2009 Jul;11(7):411-27
references.pmid: 19574199
references.citation: Pigment Cell Melanoma Res. 2010 Feb;23(1):41-56
references.pmid: 19843243
references.citation: Mol Cancer. 2006 Dec 02;5:67
references.pmid: 17140455
references.citation: Sci China C Life Sci. 2009 Jul;52(7):622-36
references.pmid: 19641867
references.citation: J Clin Invest. 2008 Jun;118(6):2111-20
references.pmid: 18497886
references.citation: J Hematother Stem Cell Res. 2001 Apr;10(2):273-81
references.pmid: 11359674
references.citation: Nature. 2008 Jul 3;454(7200):49-55
references.pmid: 18509334
references.citation: Stem Cells. 2008 Dec;26(12):3008-17
references.pmid: 18802032
references.citation: Biochem Biophys Res Commun. 2008 Apr 18;368(4):930-6
references.pmid: 18279661
references.citation: Exp Cell Res. 2004 Aug 1;298(1):144-54
references.pmid: 15242769
references.citation: Toxicol In Vitro. 2010 Mar;24(2):538-45
references.pmid: 19913610