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BMC Cancer
Published in: BMC Cancer 1/2012

Open Access 01-12-2012 | Research article

Characterization of colon cancer cells: a functional approach characterizing CD133 as a potential stem cell marker

Authors: Meike Schneider, Johannes Huber, Boris Hadaschik, Gabrielle M Siegers, Heinz-Herbert Fiebig, Julia Schüler

Published in: BMC Cancer | Issue 1/2012

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Abstract

Background

Isolation and characterization of tumourigenic colon cancer initiating cells may help to develop novel diagnostic and therapeutic procedures.

Methods

We characterized a panel of fourteen human colon carcinoma cell lines and their corresponding xenografts for the surface expression of potential stem cell markers CD133, CD24, CD44, CDCP1 and CXCR4. In five cell lines and nine xenografts, mRNA expression of these markers was determined. Tumour growth behaviour of CD133+, CD133- and unsorted SW620 cells was evaluated in vivo.

Results

All five putative stem cell markers showed distinct expression patterns in the tumours examined. Two patient-derived cell lines highly expressed CD133 (> 85% of positive cells) and three other cell lines had an expression level of about 50% whereas in long-term culture based models CD133 expression ranged only from 0 to 20%. In 8/14 cell lines, more than 80% of the cells were positive for CD24 and 11/14 were over 70% positive for CD44. 10/14 cell lines expressed CDCP1 on ≥ 83% of cells. CXCR4 expression was determined solely on 94 L and SW480.
Analyses of the corresponding xenografts revealed a significant reduction of cell numbers expressing the investigated surface markers and showed single cell fractions expressing up to three markers simultaneously.
Statistical analysis revealed that the CXCR4 mRNA level correlates negatively with the protein expression of CD133, CD44, CD24 and CDCP1 in cell lines and xenografts.
A lower differentiation grade of donor material correlated with a higher CDCP1 mRNA expression level in the respective tumour model.
In vivo growth behaviour studies of SW620 revealed significantly higher take rates and shorter doubling times in the tumour growth of CD133 positive subclones in comparison to the unsorted cell line or CD133 negative subclones.

Conclusions

Our data revealed correlations in the expression of surface markers CD44 and CD24 as well as CD44 and CDCP1 and strongly suggest that CD133 is a stem cell marker within our colon carcinoma panel. Further studies will elucidate its role as a potential therapeutic target.
Appendix
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Literature
1.
Dalerba P, Cho RW, Clarke MF: Cancer stem cells: models and concepts. Annu Rev Med. 2007, 58: 267-284. 10.1146/annurev.med.58.062105.204854.CrossRefPubMed
2.
Steeg PS: Tumor metastasis: mechanistic insights and clinical challenges. Nat Med. 2006, 12 (8): 895-904. 10.1038/nm1469.CrossRefPubMed
3.
Wang JC, Dick JE: Cancer stem cells: lessons from leukemia. Trends Cell Biol. 2005, 15 (9): 494-501. 10.1016/j.tcb.2005.07.004.CrossRefPubMed
4.
Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF: Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA. 2003, 100 (7): 3983-3988. 10.1073/pnas.0530291100.CrossRefPubMedPubMedCentral
5.
Li C, Heidt DG, Dalerba P, Burant CF, Zhang L, Adsay V, Wicha M, Clarke MF, Simeone DM: Identification of pancreatic cancer stem cells. Cancer Res. 2007, 67 (3): 1030-1037. 10.1158/0008-5472.CAN-06-2030.CrossRefPubMed
6.
Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD, Dirks PB: Identification of human brain tumour initiating cells. Nature. 2004, 432 (7015): 396-401. 10.1038/nature03128.CrossRefPubMed
7.
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 (7123): 106-110. 10.1038/nature05372.CrossRefPubMed
8.
Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C, De Maria R: Identification and expansion of human colon-cancer-initiating cells. Nature. 2007, 445 (7123): 111-115. 10.1038/nature05384.CrossRefPubMed
9.
Miraglia S, Godfrey W, Yin AH, Atkins K, Warnke R, Holden JT, Bray RA, Waller EK, Buck DW: A novel five-transmembrane hematopoietic stem cell antigen: isolation, characterization, and molecular cloning. Blood. 1997, 90 (12): 5013-5021.PubMed
10.
Mizrak D, Brittan M, Alison MR: CD133: molecule of the moment. J Pathol. 2008, 214 (1): 3-9. 10.1002/path.2283.CrossRefPubMed
11.
Keysar SB, Jimeno A: More than markers: biological significance of cancer stem cell-defining molecules. Mol Cancer Ther. 2010, 9 (9): 2450-2457. 10.1158/1535-7163.MCT-10-0530.CrossRefPubMedPubMedCentral
12.
Lim SC: CD24 and human carcinoma: tumor biological aspects. Biomed Pharmacother. 2005, 59 (Suppl 2): S351-S354.CrossRefPubMed
13.
Sano A, Kato H, Sakurai S, Sakai M, Tanaka N, Inose T, Saito K, Sohda M, Nakajima M, Nakajima T, et al: CD24 expression is a novel prognostic factor in esophageal squamous cell carcinoma. Ann Surg Oncol. 2009, 16 (2): 506-514. 10.1245/s10434-008-0252-0.CrossRefPubMed
14.
Aigner S, Sthoeger ZM, Fogel M, Weber E, Zarn J, Ruppert M, Zeller Y, Vestweber D, Stahel R, Sammar M, et al: CD24, a mucin-type glycoprotein, is a ligand for P-selectin on human tumor cells. Blood. 1997, 89 (9): 3385-3395.PubMed
15.
Baumann P, Cremers N, Kroese F, Orend G, Chiquet-Ehrismann R, Uede T, Yagita H, Sleeman JP: CD24 expression causes the acquisition of multiple cellular properties associated with tumor growth and metastasis. Cancer Res. 2005, 65 (23): 10783-10793. 10.1158/0008-5472.CAN-05-0619.CrossRefPubMed
16.
Uekita T, Jia L, Narisawa-Saito M, Yokota J, Kiyono T, Sakai R: CUB domain-containing protein 1 is a novel regulator of anoikis resistance in lung adenocarcinoma. Mol Cell Biol. 2007, 27 (21): 7649-7660. 10.1128/MCB.01246-07.CrossRefPubMedPubMedCentral
17.
Benes CH, Poulogiannis G, Cantley LC, Soltoff SP: The SRC-associated protein CUB Domain-Containing Protein-1 regulates adhesion and motility. Oncogene. 2012
18.
Kucia M, Reca R, Miekus K, Wanzeck J, Wojakowski W, Janowska-Wieczorek A, Ratajczak J, Ratajczak MZ: Trafficking of normal stem cells and metastasis of cancer stem cells involve similar mechanisms: pivotal role of the SDF-1-CXCR4 axis. Stem cells (Dayton, Ohio). 2005, 23 (7): 879-894. 10.1634/stemcells.2004-0342.CrossRef
19.
Workman P, Aboagye EO, Balkwill F, Balmain A, Bruder G, Chaplin DJ, Double JA, Everitt J, Farningham DA, Glennie MJ, et al: Guidelines for the welfare and use of animals in cancer research. Br J Cancer. 2010, 102 (11): 1555-1577. 10.1038/sj.bjc.6605642.CrossRefPubMedPubMedCentral
20.
Fiebig HH, Maier A, Burger AM: Clonogenic assay with established human tumour xenografts: correlation of in vitro to in vivo activity as a basis for anticancer drug discovery. Eur J Cancer. 2004, 40 (6): 802-820. 10.1016/j.ejca.2004.01.009.CrossRefPubMed
21.
Fiebig HH, Schuler J, Bausch N, Hofmann M, Metz T, Korrat A: Gene signatures developed from patient tumor explants grown in nude mice to predict tumor response to 11 cytotoxic drugs. CANCER GENOMICS PROTEOMICS. 2007, 4 (3): 197-209.PubMed
22.
23.
Shi L, Reid LH, Jones WD, Shippy R, Warrington JA, Baker SC, Collins PJ, de Longueville F, Kawasaki ES, Lee KY, et al: The MicroArray Quality Control (MAQC) project shows inter- and intraplatform reproducibility of gene expression measurements. Nat Biotechnol. 2006, 24 (9): 1151-1161. 10.1038/nbt1239.CrossRefPubMed
24.
Zhijin Wu, Rafael AI, Gentleman Robert, Murillo Francisco Martinez, Spencer Forrest: A Model Based Background Adjustment for Oligonucleotide Expression Arrays. 2004, Johns Hopkins University, Department of Biostatistics Working Papers, Working Paper 1
25.
Bengtsson H, Ray A, Spellman P, Speed TP: A single-sample method for normalizing and combining full-resolution copy numbers from multiple platforms, labs and analysis methods. Bioinformatics (Oxford, England). 2009, 25 (7): 861-867. 10.1093/bioinformatics/btp074.CrossRef
26.
Clarke MF, Dick JE, Dirks PB, Eaves CJ, Jamieson CH, Jones DL, Visvader J, Weissman IL, Wahl GM: Cancer stem cells-perspectives on current status and future directions: AACR Workshop on cancer stem cells. Cancer Res. 2006, 66 (19): 9339-9344. 10.1158/0008-5472.CAN-06-3126.CrossRefPubMed
27.
Reya T, Morrison SJ, Clarke MF, Weissman IL: Stem cells, cancer, and cancer stem cells. Nature. 2001, 414 (6859): 105-111. 10.1038/35102167.CrossRefPubMed
28.
Vermeulen L, Sprick MR, Kemper K, Stassi G, Medema JP: Cancer stem cells-old concepts, new insights. Cell Death Differ. 2008, 15 (6): 947-958. 10.1038/cdd.2008.20.CrossRefPubMed
29.
Matsui W, Wang Q, Barber JP, Brennan S, Smith BD, Borrello I, McNiece I, Lin L, Ambinder RF, Peacock C, et al: Clonogenic multiple myeloma progenitors, stem cell properties, and drug resistance. Cancer Res. 2008, 68 (1): 190-197. 10.1158/0008-5472.CAN-07-3096.CrossRefPubMedPubMedCentral
30.
Kelly PN, Dakic A, Adams JM, Nutt SL, Strasser A: Tumor growth need not be driven by rare cancer stem cells. Science (New York, NY). 2007, 317 (5836): 337-10.1126/science.1142596.CrossRef
31.
Li L, Xie T: Stem cell niche: structure and function. Annu Rev Cell Dev Biol. 2005, 21: 605-631. 10.1146/annurev.cellbio.21.012704.131525.CrossRefPubMed
32.
Calabrese C, Poppleton H, Kocak M, Hogg TL, Fuller C, Hamner B, Oh EY, Gaber MW, Finklestein D, Allen M, et al: A perivascular niche for brain tumor stem cells. Cancer Cell. 2007, 11 (1): 69-82. 10.1016/j.ccr.2006.11.020.CrossRefPubMed
33.
Vermeulen L, De Sousa EMF, van der Heijden M, Cameron K, de Jong JH, Borovski T, Tuynman JB, Todaro M, Merz C, Rodermond H, et al: Wnt activity defines colon cancer stem cells and is regulated by the microenvironment. Nat Cell Biol. 2003, 12 (5): 468-476.CrossRef
34.
Todaro M, Alea MP, Di Stefano AB, Cammareri P, Vermeulen L, Iovino F, Tripodo C, Russo A, Gulotta G, Medema JP, et al: Colon cancer stem cells dictate tumor growth and resist cell death by production of interleukin-4. Cell Stem Cell. 2007, 1 (4): 389-402. 10.1016/j.stem.2007.08.001.CrossRefPubMed
35.
Nikolova T, Wu M, Brumbarov K, Alt R, Opitz H, Boheler KR, Cross M, Wobus AM: WNT-conditioned media differentially affect the proliferation and differentiation of cord blood-derived CD133+ cells in vitro. Differentiation; research in biological diversity. 2007, 75 (2): 100-111. 10.1111/j.1432-0436.2006.00119.x.CrossRefPubMed
36.
Reya T, Clevers H: Wnt signalling in stem cells and cancer. Nature. 2005, 434 (7035): 843-850. 10.1038/nature03319.CrossRefPubMed
37.
Bruno S, Bussolati B, Grange C, Collino F, Graziano ME, Ferrando U, Camussi G: CD133+ renal progenitor cells contribute to tumor angiogenesis. Am J Pathol. 2006, 169 (6): 2223-2235. 10.2353/ajpath.2006.060498.CrossRefPubMedPubMedCentral
38.
Beier D, Hau P, Proescholdt M, Lohmeier A, Wischhusen J, Oefner PJ, Aigner L, Brawanski A, Bogdahn U, Beier CP: CD133(+) and CD133(-) glioblastoma-derived cancer stem cells show differential growth characteristics and molecular profiles. Cancer Res. 2007, 67 (9): 4010-4015. 10.1158/0008-5472.CAN-06-4180.CrossRefPubMed
39.
Kim J, Takeuchi H, Lam ST, Turner RR, Wang HJ, Kuo C, Foshag L, Bilchik AJ, Hoon DS: Chemokine receptor CXCR4 expression in colorectal cancer patients increases the risk for recurrence and for poor survival. J Clin Oncol. 2005, 23 (12): 2744-2753.CrossRefPubMed
40.
Yang M, Reynoso J, Bouvet M, Hoffman RM: A transgenic red fluorescent protein-expressing nude mouse for color-coded imaging of the tumor microenvironment. J Cell Biochem. 2009, 106 (2): 279-284. 10.1002/jcb.21999.CrossRefPubMedPubMedCentral
41.
Matsusue R, Kubo H, Hisamori S, Okoshi K, Takagi H, Hida K, Nakano K, Itami A, Kawada K, Nagayama S, et al: Hepatic stellate cells promote liver metastasis of colon cancer cells by the action of SDF-1/CXCR4 axis. Ann Surg Oncol. 2009, 16 (9): 2645-2653. 10.1245/s10434-009-0599-x.CrossRefPubMed
42.
Fialkow PJ, Singer JW, Raskind WH, Adamson JW, Jacobson RJ, Bernstein ID, Dow LW, Najfeld V, Veith R: Clonal development, stem-cell differentiation, and clinical remissions in acute nonlymphocytic leukemia. N Engl J Med. 1987, 317 (8): 468-473. 10.1056/NEJM198708203170802.CrossRefPubMed
43.
Xie W, Wang X, Du W, Liu W, Qin X, Huang S: Detection of molecular targets on the surface of CD34+CD38- bone marrow cells in myelodysplastic syndromes. Cytometry A. 2010, 77 (9): 840-848.CrossRefPubMed
44.
Scherl-Mostageer M, Sommergruber W, Abseher R, Hauptmann R, Ambros P, Schweifer N: Identification of a novel gene, CDCP1, overexpressed in human colorectal cancer. Oncogene. 2001, 20 (32): 4402-4408. 10.1038/sj.onc.1204566.CrossRefPubMed
45.
Uekita T, Tanaka M, Takigahira M, Miyazawa Y, Nakanishi Y, Kanai Y, Yanagihara K, Sakai R: CUB-domain-containing protein 1 regulates peritoneal dissemination of gastric scirrhous carcinoma. Am J Pathol. 2008, 172 (6): 1729-1739. 10.2353/ajpath.2008.070981.CrossRefPubMedPubMedCentral
Metadata
Title
Characterization of colon cancer cells: a functional approach characterizing CD133 as a potential stem cell marker
Authors
Meike Schneider
Johannes Huber
Boris Hadaschik
Gabrielle M Siegers
Heinz-Herbert Fiebig
Julia Schüler
Publication date
01-12-2012
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2012
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-12-96

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