Characterization of the intestinal cancer stem cell marker CD166 in the human and mouse gastrointestinal tract.
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.
Levin
Trevor G
TG
Department of Cell and Developmental Biology, Knight Cancer Institute, Oregon Stem Cell Center, Portland, Oregon, USA.
Powell
Anne E
AE
Davies
Paige S
PS
Silk
Alain D
AD
Dismuke
Adria D
AD
Anderson
Eric C
EC
Swain
John R
JR
Wong
Melissa H
MH
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
D015703:Antigens, CD; D014408:Biomarkers, Tumor; D015816:Cell Adhesion Molecules, Neuronal; D005326:Fetal Proteins; C105613:ALCAM protein, human; D020410:Activated-Leukocyte Cell Adhesion Molecule
Blood. 1997 Apr 15;89(8):2706-16
9108388
J Bone Miner Res. 1998 Apr;13(4):655-63
9556065
Mod Pathol. 2007 Jan;20(1):102-7
17143262
Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):3983-8
12629218
Science. 1976 Oct 1;194(4260):23-8
959840
J Biol Chem. 1993 Aug 25;268(24):18345-58
8349710
Nat Rev Cancer. 2003 Dec;3(12):895-902
14737120
Science. 2008 Jan 18;319(5861):336-9
18202291
Cancer Res. 2009 Apr 15;69(8):3382-9
19336570
J Neurobiol. 1994 Jul;25(7):831-45
8089660
J Exp Med. 1995 Apr 1;181(4):1563-8
7535342
Am J Pathol. 2000 Mar;156(3):769-74
10702391
J Cell Biol. 1998 May 4;141(3):765-77
9566975
Proc Natl Acad Sci U S A. 2007 Jun 12;104(24):10158-63
17548814
Nat Cell Biol. 2008 Mar;10(3):353-60
18264089
Nature. 2009 May 14;459(7244):262-5
19329995
J Cell Sci. 2005 Apr 1;118(Pt 7):1515-25
15769845
BMC Gastroenterol. 2008 Dec 02;8:57
19055726
Cell. 2009 Mar 6;136(5):903-12
19269367
Cancer Metastasis Rev. 2000;19(3-4):I-XI, 193-383
11394186
Nat Immunol. 2008 Feb;9(2):137-45
18157132
Eur J Immunol. 2004 Apr;34(4):930-40
15048703
Cell Stem Cell. 2009 May 8;4(5):427-39
19427292
Mol Cancer Ther. 2007 Oct;6(10):2737-46
17938267
Curr Opin Genet Dev. 2008 Feb;18(1):48-53
18356041
Am J Pathol. 1998 Mar;152(3):805-13
9502422
J Clin Pathol. 2004 Nov;57(11):1160-4
15509676
Differentiation. 2003 Jan;71(1):28-41
12558601
Exp Cell Res. 1992 Nov;203(1):91-9
1426054
J Biol Chem. 2004 Dec 31;279(53):55315-23
15496415
Nat Genet. 2008 Jul;40(7):915-20
18536716
Stem Cells. 2008 Mar;26(3):630-7
18055444
Science. 1990 Jan 19;247(4940):322-4
2296722
J Clin Pathol. 2006 Apr;59(4):403-9
16484444
FEBS Lett. 2006 May 15;580(11):2637-45
16650408
Prostate. 2003 Jan 1;54(1):34-43
12481253
Am J Physiol Gastrointest Liver Physiol. 2010 May;298(5):G590-600
20185687
Nature. 2007 Oct 25;449(7165):1003-7
17934449
Oncology. 2005;68(4-6):462-70
16024937
Cell Death Differ. 2008 Jun;15(6):947-58
18259194
J Exp Med. 1995 Jun 1;181(6):2213-20
7760007
J Exp Med. 2002 Jun 17;195(12):1549-63
12070283
Nature. 2007 Jan 4;445(7123):106-10
17122772
Development. 2007 Apr;134(8):1491-7
17344225
Nature. 2006 Jan 5;439(7072):84-8
16397499
J Immunol. 2006 Jul 15;177(2):877-84
16818742
Blood. 2001 Oct 1;98(7):2134-42
11568000
Med Sci Monit. 2006 Aug;12(8):BR263-73
16865058
Cancer Res. 2007 Feb 1;67(3):1030-7
17283135
PLoS One. 2008 Jun 18;3(6):e2428
18560594
Clin Cancer Res. 2008 Mar 15;14(6):1726-33
18347173