title: Characterization of the intestinal cancer stem cell marker CD166 in the human and mouse gastrointestinal tract.
abstract: OBJECTIVE
  CD166 (also called activated leukocyte cell adhesion molecule [ALCAM]) is a marker of colorectal cancer (CRC) stem cells; it is expressed by aggressive tumors. Although the presence of CD166 at the tumor cell surface has been correlated with shortened survival, little is known about its function and expression in normal intestinal epithelia.
  
  
  METHODS
  We characterized the expression pattern of CD166 in normal intestinal tissue samples from humans and mice using immunohistochemisty, flow cytometry, and quantitative reverse-transcriptase polymerase chain reaction. Human and mouse intestinal tumors were also analyzed.
  
  
  RESULTS
  CD166 was expressed on the surface of epithelial cells within the stem cell niche and along the length of the intestine; expression was conserved across species. In the small intestine, CD166 was observed on crypt-based Paneth cells and intervening crypt-based columnar cells (putative stem cells). A subset of CD166-positive, crypt-based columnar cells coexpressed the stem cell markers Lgr5, Musashi-1, or Dcamkl-1. CD166 was located in the cytoplasm and at the surface of cells within human CRC tumors. CD166-positive cells were also detected in benign adenomas in mice; rare cells coexpressed CD166 and CD44 or epithelial-specific antigen.
  
  
  CONCLUSIONS
  CD166 is highly expressed within the endogenous intestinal stem cell niche. CD166-positive cells appear at multiple stages of intestinal carcinoma progression, including benign and metastatic tumors. Further studies should investigate the function of CD166 in stem cells and the stem cell niche, which might have implications for normal intestinal homeostasis. CD166 has potential as a therapeutic target for CRC.
authors.affiliation: Department of Cell and Developmental Biology, Knight Cancer Institute, Oregon Stem Cell Center, Portland, Oregon, USA.
authors.forename: Trevor G
authors.initials: TG
authors.lastname: Levin
authors.forename: Anne E
authors.initials: AE
authors.lastname: Powell
authors.forename: Paige S
authors.initials: PS
authors.lastname: Davies
authors.forename: Alain D
authors.initials: AD
authors.lastname: Silk
authors.forename: Adria D
authors.initials: AD
authors.lastname: Dismuke
authors.forename: Eric C
authors.initials: EC
authors.lastname: Anderson
authors.forename: John R
authors.initials: JR
authors.lastname: Swain
authors.forename: Melissa H
authors.initials: MH
authors.lastname: Wong
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000556:secondary; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D001706:Biopsy; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D003106:Colon / Q000166:cytology / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D005326:Fetal Proteins / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism*; D007421:Intestine, Small / Q000166:cytology / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D020410:Activated-Leukocyte Cell Adhesion Molecule
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; D015816:Cell Adhesion Molecules, Neuronal; D005326:Fetal Proteins; C105613:ALCAM protein, human; D020410:Activated-Leukocyte Cell Adhesion Molecule
references.citation: Blood. 1997 Apr 15;89(8):2706-16
references.pmid: 9108388
references.citation: J Bone Miner Res. 1998 Apr;13(4):655-63
references.pmid: 9556065
references.citation: Mod Pathol. 2007 Jan;20(1):102-7
references.pmid: 17143262
references.citation: Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):3983-8
references.pmid: 12629218
references.citation: Science. 1976 Oct 1;194(4260):23-8
references.pmid: 959840
references.citation: J Biol Chem. 1993 Aug 25;268(24):18345-58
references.pmid: 8349710
references.citation: Nat Rev Cancer. 2003 Dec;3(12):895-902
references.pmid: 14737120
references.citation: Science. 2008 Jan 18;319(5861):336-9
references.pmid: 18202291
references.citation: Cancer Res. 2009 Apr 15;69(8):3382-9
references.pmid: 19336570
references.citation: J Neurobiol. 1994 Jul;25(7):831-45
references.pmid: 8089660
references.citation: J Exp Med. 1995 Apr 1;181(4):1563-8
references.pmid: 7535342
references.citation: Am J Pathol. 2000 Mar;156(3):769-74
references.pmid: 10702391
references.citation: J Cell Biol. 1998 May 4;141(3):765-77
references.pmid: 9566975
references.citation: Proc Natl Acad Sci U S A. 2007 Jun 12;104(24):10158-63
references.pmid: 17548814
references.citation: Nat Cell Biol. 2008 Mar;10(3):353-60
references.pmid: 18264089
references.citation: Nature. 2009 May 14;459(7244):262-5
references.pmid: 19329995
references.citation: J Cell Sci. 2005 Apr 1;118(Pt 7):1515-25
references.pmid: 15769845
references.citation: BMC Gastroenterol. 2008 Dec 02;8:57
references.pmid: 19055726
references.citation: Cell. 2009 Mar 6;136(5):903-12
references.pmid: 19269367
references.citation: Cancer Metastasis Rev. 2000;19(3-4):I-XI, 193-383
references.pmid: 11394186
references.citation: Nat Immunol. 2008 Feb;9(2):137-45
references.pmid: 18157132
references.citation: Eur J Immunol. 2004 Apr;34(4):930-40
references.pmid: 15048703
references.citation: Cell Stem Cell. 2009 May 8;4(5):427-39
references.pmid: 19427292
references.citation: Mol Cancer Ther. 2007 Oct;6(10):2737-46
references.pmid: 17938267
references.citation: Curr Opin Genet Dev. 2008 Feb;18(1):48-53
references.pmid: 18356041
references.citation: Am J Pathol. 1998 Mar;152(3):805-13
references.pmid: 9502422
references.citation: J Clin Pathol. 2004 Nov;57(11):1160-4
references.pmid: 15509676
references.citation: Differentiation. 2003 Jan;71(1):28-41
references.pmid: 12558601
references.citation: Exp Cell Res. 1992 Nov;203(1):91-9
references.pmid: 1426054
references.citation: J Biol Chem. 2004 Dec 31;279(53):55315-23
references.pmid: 15496415
references.citation: Nat Genet. 2008 Jul;40(7):915-20
references.pmid: 18536716
references.citation: Stem Cells. 2008 Mar;26(3):630-7
references.pmid: 18055444
references.citation: Science. 1990 Jan 19;247(4940):322-4
references.pmid: 2296722
references.citation: J Clin Pathol. 2006 Apr;59(4):403-9
references.pmid: 16484444
references.citation: FEBS Lett. 2006 May 15;580(11):2637-45
references.pmid: 16650408
references.citation: Prostate. 2003 Jan 1;54(1):34-43
references.pmid: 12481253
references.citation: Am J Physiol Gastrointest Liver Physiol. 2010 May;298(5):G590-600
references.pmid: 20185687
references.citation: Nature. 2007 Oct 25;449(7165):1003-7
references.pmid: 17934449
references.citation: Oncology. 2005;68(4-6):462-70
references.pmid: 16024937
references.citation: Cell Death Differ. 2008 Jun;15(6):947-58
references.pmid: 18259194
references.citation: J Exp Med. 1995 Jun 1;181(6):2213-20
references.pmid: 7760007
references.citation: J Exp Med. 2002 Jun 17;195(12):1549-63
references.pmid: 12070283
references.citation: Nature. 2007 Jan 4;445(7123):106-10
references.pmid: 17122772
references.citation: Development. 2007 Apr;134(8):1491-7
references.pmid: 17344225
references.citation: Nature. 2006 Jan 5;439(7072):84-8
references.pmid: 16397499
references.citation: J Immunol. 2006 Jul 15;177(2):877-84
references.pmid: 16818742
references.citation: Blood. 2001 Oct 1;98(7):2134-42
references.pmid: 11568000
references.citation: Med Sci Monit. 2006 Aug;12(8):BR263-73
references.pmid: 16865058
references.citation: Cancer Res. 2007 Feb 1;67(3):1030-7
references.pmid: 17283135
references.citation: PLoS One. 2008 Jun 18;3(6):e2428
references.pmid: 18560594
references.citation: Clin Cancer Res. 2008 Mar 15;14(6):1726-33
references.pmid: 18347173