Biological and genetic characteristics of tumor-initiating cells in colon cancer.
BACKGROUND
Human prominin-1 (PROM1, CD133) was used as a marker to detect stem cells (progenitor cells) and cancer stem cells (tumor-initiating cells) in various tissues. The purpose of this study was to investigate the biological and genetic characteristics of tumor-initiating cells in colon cancer with both in vitro and in vivo analyses.


METHODS
The CD133 expression of 12 colon cancer cell lines was evaluated. CD133+ cells were isolated by flow cytometry and examined for in vivo tumor formation, in vitro proliferation, colony formation, and invasion ability. Additionally, we used microarray analysis to compare gene expression profiles between CD133+ and CD133- isolated cells.


RESULTS
CD133+ cells were found in 5 of 12 colon cancer cell lines. Isolated CD133+ cells from the HT29 colon cancer cell line exhibited a higher tumorigenic potential than CD133- cells in the in vivo tumor formation assay. Furthermore, it was shown that CD133+ cells are more proliferative and have higher colony-forming and invasive abilities than CD133- cells in vitro. Microarray analysis found differential gene expression correlating with CD133 expression.


CONCLUSIONS
It was confirmed that CD133+ cells in colon cancer are useful markers for the detection of tumor-initiating cells. Intimate biological and genetic features of CD133+ cells in colon cancer cell lines were also revealed. The biological characteristics of CD133+ cells and differentially expressed genes in these cells will help elucidate more details of tumor-initiating cells in colon cancer.
Ieta
Keisuke
K
Department of Surgery and Molecular Oncology, Medical Institute of Bioregulation, Kyushu University, 4546 Tsurumihara, Beppu 874-0838, Japan.
Tanaka
Fumiaki
F
Haraguchi
Naotsugu
N
Kita
Yoshiaki
Y
Sakashita
Hiroyuki
H
Mimori
Koshi
K
Matsumoto
Toshifumi
T
Inoue
Hiroshi
H
Kuwano
Hiroyuki
H
Mori
Masaki
M
D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000235:genetics / Q000503:physiopathology*; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006023:Glycoproteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D010455:Peptides / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells
D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse