BACKGROUND & AIMS: 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.
BACKGROUND & AIMS: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 mouseintestinal 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 humanCRC 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: S P Bruder; N S Ricalton; R E Boynton; T J Connolly; N Jaiswal; J Zaia; F P Barry Journal: J Bone Miner Res Date: 1998-04 Impact factor: 6.741
Authors: W G Degen; L C van Kempen; E G Gijzen; J J van Groningen; Y van Kooyk; H P Bloemers; G W Swart Journal: Am J Pathol Date: 1998-03 Impact factor: 4.307
Authors: Christopher S Potten; Catherine Booth; Gregory L Tudor; Dawn Booth; Gerard Brady; Patricia Hurley; Gary Ashton; Robert Clarke; Shin-ichi Sakakibara; Hideyuki Okano Journal: Differentiation Date: 2003-01 Impact factor: 3.880
Authors: M A Bowen; D D Patel; X Li; B Modrell; A R Malacko; W C Wang; H Marquardt; M Neubauer; J M Pesando; U Francke Journal: J Exp Med Date: 1995-06-01 Impact factor: 14.307
Authors: Kelley S Yan; Luis A Chia; Xingnan Li; Akifumi Ootani; James Su; Josephine Y Lee; Nan Su; Yuling Luo; Sarah C Heilshorn; Manuel R Amieva; Eugenio Sangiorgi; Mario R Capecchi; Calvin J Kuo Journal: Proc Natl Acad Sci U S A Date: 2011-12-21 Impact factor: 11.205
Authors: Seema Bhatlekar; Sankar Addya; Moreh Salunek; Christopher R Orr; Saul Surrey; Steven McKenzie; Jeremy Z Fields; Bruce M Boman Journal: Stem Cells Dev Date: 2013-11-05 Impact factor: 3.272
Authors: Linlin Xu; Khalid S Mohammad; Hao Wu; Colin Crean; Bradley Poteat; Yinghua Cheng; Angelo A Cardoso; Christophe Machal; Helmut Hanenberg; Rafat Abonour; Melissa A Kacena; John Chirgwin; Attaya Suvannasankha; Edward F Srour Journal: Cancer Res Date: 2016-09-07 Impact factor: 12.701