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Erschienen in: Annals of Surgical Oncology 2/2008

01.02.2008 | Gastrointestinal Oncology

Biological and Genetic Characteristics of Tumor-Initiating Cells in Colon Cancer

verfasst von: Keisuke Ieta, MD, PhD, Fumiaki Tanaka, MD, PhD, Naotsugu Haraguchi, MD, PhD, Yoshiaki Kita, MD, Hiroyuki Sakashita, MD, Koshi Mimori, MD, PhD, Toshifumi Matsumoto, MD, PhD, Hiroshi Inoue, MD, PhD, Hiroyuki Kuwano, MD, PhD, Masaki Mori, MD, PhD

Erschienen in: Annals of Surgical Oncology | Ausgabe 2/2008

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Abstract

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.
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Literatur
1.
2.
Zurück zum Zitat Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature 2001;414:105–11PubMedCrossRef Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature 2001;414:105–11PubMedCrossRef
3.
5.
Zurück zum Zitat Pardal R, Clarke MF, Morrison SJ. Applying the principles of stem-cell biology to cancer. Nat Rev Cancer 2003;3:895–902PubMedCrossRef Pardal R, Clarke MF, Morrison SJ. Applying the principles of stem-cell biology to cancer. Nat Rev Cancer 2003;3:895–902PubMedCrossRef
6.
Zurück zum Zitat Lapidot T, Sirard C, Vormoor J, et al. A cell initiating human acute myeloid leukemia after transplantation into SCID mice. Nature 1994;367:645–8PubMedCrossRef Lapidot T, Sirard C, Vormoor J, et al. A cell initiating human acute myeloid leukemia after transplantation into SCID mice. Nature 1994;367:645–8PubMedCrossRef
7.
Zurück zum Zitat Wulf GG, Wang RY, Kuehnle I, et al. A leukemic stem cell with intrinsic drug efflux capacity in acute myeloid leukemia. Blood 2001;98:1166–73PubMedCrossRef Wulf GG, Wang RY, Kuehnle I, et al. A leukemic stem cell with intrinsic drug efflux capacity in acute myeloid leukemia. Blood 2001;98:1166–73PubMedCrossRef
8.
Zurück zum Zitat Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A 2003;100:3983–8PubMedCrossRef Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A 2003;100:3983–8PubMedCrossRef
9.
Zurück zum Zitat Prince ME, Sivanandan R, Kaczorowski A, et al. Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proc Natl Acad Sci U S A 2007;104:973–8PubMedCrossRef Prince ME, Sivanandan R, Kaczorowski A, et al. Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proc Natl Acad Sci U S A 2007;104:973–8PubMedCrossRef
10.
Zurück zum Zitat Li C, Heidt DG, Dalerba P, et al. Identification of pancreatic cancer stem cells. Cancer Res 2007;67:1030–7PubMedCrossRef Li C, Heidt DG, Dalerba P, et al. Identification of pancreatic cancer stem cells. Cancer Res 2007;67:1030–7PubMedCrossRef
11.
Zurück zum Zitat Haraguchi N, Utsunomiya T, Inoue H, et al. Characterization of a side population of cancer cells from human gastrointestinal system. Stem Cells 2006;24:506–13PubMedCrossRef Haraguchi N, Utsunomiya T, Inoue H, et al. Characterization of a side population of cancer cells from human gastrointestinal system. Stem Cells 2006;24:506–13PubMedCrossRef
12.
Zurück zum Zitat Shmelkov SV, St Clair R, Lyden D, Rafii S. AC133/CD133/prominin-1. Int J Biochem Cell Biol 2005;37:715–9PubMedCrossRef Shmelkov SV, St Clair R, Lyden D, Rafii S. AC133/CD133/prominin-1. Int J Biochem Cell Biol 2005;37:715–9PubMedCrossRef
13.
Zurück zum Zitat Peichev M, Naiyer AJ, Pereira D, et al. Expression of VEGFR-2 and AC133 by circulating human CD34(+) cells identifies a population of functional endothelial precursors. Blood 2000;95:952–8PubMed Peichev M, Naiyer AJ, Pereira D, et al. Expression of VEGFR-2 and AC133 by circulating human CD34(+) cells identifies a population of functional endothelial precursors. Blood 2000;95:952–8PubMed
14.
Zurück zum Zitat Yin AH, Miraglia S, Zanjani ED, et al. AC133, a novel marker for human hematopoietic stem and progenitor cells. Blood 1997;90:5002–12PubMed Yin AH, Miraglia S, Zanjani ED, et al. AC133, a novel marker for human hematopoietic stem and progenitor cells. Blood 1997;90:5002–12PubMed
15.
Zurück zum Zitat Uchida N, Buck DW, He D, et al. Direct isolation of human central nervous system stem cells. Proc Natl Acad Sci U S A 2000;97:14720–5PubMedCrossRef Uchida N, Buck DW, He D, et al. Direct isolation of human central nervous system stem cells. Proc Natl Acad Sci U S A 2000;97:14720–5PubMedCrossRef
16.
Zurück zum Zitat Corbeil D, Roper K, Hellwig A, et al. The human AC133 hematopoietic stem cell antigen is also expressed in epithelial cells and targeted to plasma membrane protrusions. J Biol Chem 2000;275:5512–20PubMedCrossRef Corbeil D, Roper K, Hellwig A, et al. The human AC133 hematopoietic stem cell antigen is also expressed in epithelial cells and targeted to plasma membrane protrusions. J Biol Chem 2000;275:5512–20PubMedCrossRef
17.
Zurück zum Zitat Weigmann A, Corbeil D, Hellwig A, Huttner WB. Prominin, a novel microvilli-specific polytopic membrane protein of the apical surface of epithelial cells, is targeted to plasmalemmal protrusions of non-epithelial cells. Proc Natl Acad Sci U S A 1997;94:12425–30PubMedCrossRef Weigmann A, Corbeil D, Hellwig A, Huttner WB. Prominin, a novel microvilli-specific polytopic membrane protein of the apical surface of epithelial cells, is targeted to plasmalemmal protrusions of non-epithelial cells. Proc Natl Acad Sci U S A 1997;94:12425–30PubMedCrossRef
18.
Zurück zum Zitat Richardson GD, Robson CN, Lang SH, Neal DE, Maitland NJ, Collins AT. CD133, a novel marker for human prostatic epithelial stem cells. J Cell Sci 2004;117:3539–45PubMedCrossRef Richardson GD, Robson CN, Lang SH, Neal DE, Maitland NJ, Collins AT. CD133, a novel marker for human prostatic epithelial stem cells. J Cell Sci 2004;117:3539–45PubMedCrossRef
19.
Zurück zum Zitat Torrente Y, Belicchi M, Sampaolesi M, et al. Human circulating AC133(+) stem cells restore dystrophin expression and ameliorate function in dystrophic skeletal muscle. J Clin Invest 2004;114:182–95PubMed Torrente Y, Belicchi M, Sampaolesi M, et al. Human circulating AC133(+) stem cells restore dystrophin expression and ameliorate function in dystrophic skeletal muscle. J Clin Invest 2004;114:182–95PubMed
20.
Zurück zum Zitat Maw MA, Corbeil D, Koch J, et al. A frameshift mutation in prominin (mouse)-like 1 causes human retinal degeneration. Hum Mol Genet 2000;9:27–34PubMedCrossRef Maw MA, Corbeil D, Koch J, et al. A frameshift mutation in prominin (mouse)-like 1 causes human retinal degeneration. Hum Mol Genet 2000;9:27–34PubMedCrossRef
21.
Zurück zum Zitat Miraglia S, Godfrey W, Yin AH, et al. A novel five-transmembrane hematopoietic stem cell antigen: isolation, characterization, and molecular cloning. Blood 1997;90:5013–21PubMed Miraglia S, Godfrey W, Yin AH, et al. A novel five-transmembrane hematopoietic stem cell antigen: isolation, characterization, and molecular cloning. Blood 1997;90:5013–21PubMed
22.
Zurück zum Zitat Bhatia M. AC133 expression in human stem cells. Leukemia 2001;15:1685–8PubMed Bhatia M. AC133 expression in human stem cells. Leukemia 2001;15:1685–8PubMed
23.
Zurück zum Zitat Singh SK, Clarke ID, Terasaki M, et al. Identification of a cancer stem cell in human brain tumors. Cancer Res 2003;63:5821–8PubMed Singh SK, Clarke ID, Terasaki M, et al. Identification of a cancer stem cell in human brain tumors. Cancer Res 2003;63:5821–8PubMed
24.
Zurück zum Zitat Singh SK, Hawkins C, Clarke ID, et al. Identification of human brain tumour initiating cells. Nature 2004;432:396–401PubMedCrossRef Singh SK, Hawkins C, Clarke ID, et al. Identification of human brain tumour initiating cells. Nature 2004;432:396–401PubMedCrossRef
25.
Zurück zum Zitat Yin S, Li J, Hu C, et al. CD133 positive hepatocellular carcinoma cells possess high capacity for tumorigenicity. Int J Cancer 2007;120:1436–42CrossRef Yin S, Li J, Hu C, et al. CD133 positive hepatocellular carcinoma cells possess high capacity for tumorigenicity. Int J Cancer 2007;120:1436–42CrossRef
26.
Zurück zum Zitat O’Brien CA, Pollett A, Gallinger S, Dick JE. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 2007;445:106–10PubMedCrossRef O’Brien CA, Pollett A, Gallinger S, Dick JE. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 2007;445:106–10PubMedCrossRef
27.
Zurück zum Zitat Ricci-Vitiani L, Lombardi DG, Pilozzi E, et al. Identification and expansion of human colon-cancer-initiating cells. Nature 2007;445:111–5PubMedCrossRef Ricci-Vitiani L, Lombardi DG, Pilozzi E, et al. Identification and expansion of human colon-cancer-initiating cells. Nature 2007;445:111–5PubMedCrossRef
28.
Zurück zum Zitat Mori M, Mimori K, Yoshikawa Y, et al. Analysis of the gene-expression profile regarding the progression of human gastric carcinoma. Surgery 2002;131:S39–47PubMedCrossRef Mori M, Mimori K, Yoshikawa Y, et al. Analysis of the gene-expression profile regarding the progression of human gastric carcinoma. Surgery 2002;131:S39–47PubMedCrossRef
29.
Zurück zum Zitat Ogawa K, Utsunomiya T, Mimori K, et al. Clinical significance of human kallikrein gene 6 messenger RNA expression in colorectal cancer. Clin Cancer Res 2005;11:2889–93PubMedCrossRef Ogawa K, Utsunomiya T, Mimori K, et al. Clinical significance of human kallikrein gene 6 messenger RNA expression in colorectal cancer. Clin Cancer Res 2005;11:2889–93PubMedCrossRef
30.
Zurück zum Zitat Albini A, Iwamoto Y, Kleinman HK, et al. A rapid in vitro assay for quantitating the invasive potential of tumor cells. Cancer Res 1987;47:3239–45PubMed Albini A, Iwamoto Y, Kleinman HK, et al. A rapid in vitro assay for quantitating the invasive potential of tumor cells. Cancer Res 1987;47:3239–45PubMed
31.
Zurück zum Zitat Nishida K, Mine S, Utsunomiya T, et al. Global analysis of altered gene expressions during the process of esophageal squamous cell carcinogenesis in the rat: a study combined with a laser microdissection and a cDNA microarray. Cancer Res 2005;65:401–9PubMed Nishida K, Mine S, Utsunomiya T, et al. Global analysis of altered gene expressions during the process of esophageal squamous cell carcinogenesis in the rat: a study combined with a laser microdissection and a cDNA microarray. Cancer Res 2005;65:401–9PubMed
32.
Zurück zum Zitat Quackenbush J. Microarray data normalization and transformation. Nat Genet 2002;32:496501CrossRef Quackenbush J. Microarray data normalization and transformation. Nat Genet 2002;32:496501CrossRef
33.
Zurück zum Zitat Brazma A, Hingamp P, Quackenbush J, et al. Minimum information about a microarray experiment (MIAME)-toward standards for microarray data. Nat Genet 2001;29:365–71PubMedCrossRef Brazma A, Hingamp P, Quackenbush J, et al. Minimum information about a microarray experiment (MIAME)-toward standards for microarray data. Nat Genet 2001;29:365–71PubMedCrossRef
34.
Zurück zum Zitat Hochberg Y, Benjamini Y. More powerful procedures for multiple significance testing. Stat Med 1990;9:811–8PubMedCrossRef Hochberg Y, Benjamini Y. More powerful procedures for multiple significance testing. Stat Med 1990;9:811–8PubMedCrossRef
35.
Zurück zum Zitat Ponti D, Costa A, Zaffaroni N, et al. Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/progenitor cell properties. Cancer Res 2005;65:5506–11PubMedCrossRef Ponti D, Costa A, Zaffaroni N, et al. Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/progenitor cell properties. Cancer Res 2005;65:5506–11PubMedCrossRef
36.
Zurück zum Zitat Kondo T, Setoguchi T, Taga T. Persistence of a small subpopulation of cancer stem-like cells in the C6 glioma cell line. Proc Natl Acad Sci U S A 2004;101:781–6PubMedCrossRef Kondo T, Setoguchi T, Taga T. Persistence of a small subpopulation of cancer stem-like cells in the C6 glioma cell line. Proc Natl Acad Sci U S A 2004;101:781–6PubMedCrossRef
37.
Zurück zum Zitat Suetsugu A, Nagaki M, Aoki H, Motohashi T, Kunisada T, Moriwaki H. Characterization of CD133+ hepatocellular carcinoma cells as cancer stem/progenitor cells. Biochem Biophys Res Commun 2006;351:820–4PubMedCrossRef Suetsugu A, Nagaki M, Aoki H, Motohashi T, Kunisada T, Moriwaki H. Characterization of CD133+ hepatocellular carcinoma cells as cancer stem/progenitor cells. Biochem Biophys Res Commun 2006;351:820–4PubMedCrossRef
38.
Zurück zum Zitat Blazek ER, Foutch JL, Maki G. Daoy medulloblastoma cells that express CD133 are radioresistant relative to CD133- cells, and the CD133+ sector is enlarged by hypoxia. Int J Radiat Oncol Biol Phys 2007;67:1–5PubMed Blazek ER, Foutch JL, Maki G. Daoy medulloblastoma cells that express CD133 are radioresistant relative to CD133- cells, and the CD133+ sector is enlarged by hypoxia. Int J Radiat Oncol Biol Phys 2007;67:1–5PubMed
39.
Zurück zum Zitat Liu G, Yuan X, Zeng Z, et al. Analysis of gene expression and chemoresistance of CD133+ cancer stem cells in glioblastoma. Mol Cancer 2006;5:67PubMedCrossRef Liu G, Yuan X, Zeng Z, et al. Analysis of gene expression and chemoresistance of CD133+ cancer stem cells in glioblastoma. Mol Cancer 2006;5:67PubMedCrossRef
40.
Zurück zum Zitat Bao S, Wu Q, McLendon RE, et al. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 2006;444:756–60PubMedCrossRef Bao S, Wu Q, McLendon RE, et al. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 2006;444:756–60PubMedCrossRef
42.
Zurück zum Zitat Blau HM, Brazelton TR, Weimann JM. The evolving concept of a stem cell: entity or function? Cell 2001;105:829–41PubMedCrossRef Blau HM, Brazelton TR, Weimann JM. The evolving concept of a stem cell: entity or function? Cell 2001;105:829–41PubMedCrossRef
43.
Zurück zum Zitat De Paiva CS, Pflugfelder SC, Li DQ. Cell size correlates with phenotype and proliferative capacity in human corneal epithelial cells. Stem Cells 2006;24:368–75PubMedCrossRef De Paiva CS, Pflugfelder SC, Li DQ. Cell size correlates with phenotype and proliferative capacity in human corneal epithelial cells. Stem Cells 2006;24:368–75PubMedCrossRef
44.
Zurück zum Zitat Dalerba P, Dylla SJ, Park IK, et al. Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci U S A 2007;104:10158–63PubMedCrossRef Dalerba P, Dylla SJ, Park IK, et al. Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci U S A 2007;104:10158–63PubMedCrossRef
45.
Zurück zum Zitat Arai F, Hirao A, Ohmura M, et al. Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche. Cell 2004;118:149–61PubMedCrossRef Arai F, Hirao A, Ohmura M, et al. Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche. Cell 2004;118:149–61PubMedCrossRef
46.
Zurück zum Zitat Grozdanov PN, Yovchev MI, Dabeva MD. The oncofetal protein glypican-3 is a novel marker of hepatic progenitor/oval cells. Lab Invest 2006;86:1272–84PubMedCrossRef Grozdanov PN, Yovchev MI, Dabeva MD. The oncofetal protein glypican-3 is a novel marker of hepatic progenitor/oval cells. Lab Invest 2006;86:1272–84PubMedCrossRef
47.
Zurück zum Zitat Ford-Perriss M, Turner K, Guimond S, et al. Localisation of specific heparan sulfate proteoglycans during the proliferative phase of brain development. Dev Dyn 2003;227:170–84PubMedCrossRef Ford-Perriss M, Turner K, Guimond S, et al. Localisation of specific heparan sulfate proteoglycans during the proliferative phase of brain development. Dev Dyn 2003;227:170–84PubMedCrossRef
Metadaten
Titel
Biological and Genetic Characteristics of Tumor-Initiating Cells in Colon Cancer
verfasst von
Keisuke Ieta, MD, PhD
Fumiaki Tanaka, MD, PhD
Naotsugu Haraguchi, MD, PhD
Yoshiaki Kita, MD
Hiroyuki Sakashita, MD
Koshi Mimori, MD, PhD
Toshifumi Matsumoto, MD, PhD
Hiroshi Inoue, MD, PhD
Hiroyuki Kuwano, MD, PhD
Masaki Mori, MD, PhD
Publikationsdatum
01.02.2008
Verlag
Springer-Verlag
Erschienen in
Annals of Surgical Oncology / Ausgabe 2/2008
Print ISSN: 1068-9265
Elektronische ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-007-9605-3

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