CD133+CD44+ population efficiently enriches colon cancer initiating cells.
BACKGROUND
Previous reports have demonstrated that CD133(+) cells or CD44(+) cells might be cancer initiating cells (CIC) of colon cancer. However, the association between the two cell types is unclear. In this study, we evaluated the tumorigenicity of each population of human colon cancer divided by CD133 and CD44 using non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice.


METHODS
Using the colon cancer cell lines HT29 and Caco2 we evaluated the change of expression status of CD133 or CD44 by a treatment with sodium butyrate (NaBT) that can induce cellular differentiation. Next, we prepared ten clinical samples of colon cancer and analyzed the expression and tumorigenicity of CD133 and CD44.


RESULTS
With NaBT treatment, CD44 expression was greatly downregulated in both HT29 and Caco2 (HT29: nontreatment versus treatment; 77.8% versus 0.6%, Caco2: 14.0% versus 0.4%, respectively), more than CD133 expression (HT29: nontreatment versus treatment; 90.1% versus 67.7%, Caco2: 98.9% versus 76.3%, respectively). In clinical samples, the percentages of CD133(+) cells and CD44(+) cells varied from 0.3% to 82.0% (mean 35.5%), and from 11.5% to 58.4% (mean 30.0%), respectively. Subcutaneous injection of CD133(+) or CD44(+) cells made a tumor in all mice (3/3 and 4/4, respectively). The combined analysis of CD133 and CD44 revealed that only the CD133(+)CD44(+) population had the ability to produce a tumor (3/3).


CONCLUSIONS
The findings demonstrate that, at present, the CD133(+)CD44(+ ) population may be the best to identify tumor initiating cells of human colon cancer.
Haraguchi
Naotsugu
N
Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, 565-0871, Japan.
Ohkuma
Masahisa
M
Sakashita
Hiroyuki
H
Matsuzaki
Shinji
S
Tanaka
Fumiaki
F
Mimori
Koshi
K
Kamohara
Yukio
Y
Inoue
Hiroshi
H
Mori
Masaki
M
D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D014408:Biomarkers, Tumor; D002087:Butyrates / Q000494:pharmacology; D002454:Cell Differentiation; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000473:pathology*; D010455:Peptides / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
D000071916:AC133 Antigen; D015703:Antigens, CD; D014408:Biomarkers, Tumor; D002087:Butyrates; D006023:Glycoproteins; D018960:Hyaluronan Receptors; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse