Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
International Journal of Oncology
Join Editorial Board Propose a Special Issue
Print ISSN: 1019-6439 Online ISSN: 1791-2423
Journal Cover
December 2012 Volume 41 Issue 6

Full Size Image

Cover Legend PDF

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
December 2012 Volume 41 Issue 6

Full Size Image

Cover Legend PDF

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

Established breast cancer stem cell markers do not correlate with in vivo tumorigenicity of tumor-initiating cells

  • Authors:
    • Christian Lehmann
    • Gabriele Jobs
    • Markus Thomas
    • Helmut Burtscher
    • Manfred Kubbies
  • View Affiliations / Copyright

    Affiliations: Discovery Oncology, Roche Diagnostics GmbH, D-82377 Penzberg, Germany
    Copyright: © Lehmann et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 1932-1942
    |
    Published online on: October 5, 2012
       https://doi.org/10.3892/ijo.2012.1654
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

The tumor-initiating capacity of primary human breast cancer cells is maintained in vitro by culturing these cells as spheres/aggregates. Inoculation of small cell numbers derived from these non-adherent cultures leads to rapid xenograft tumor formation in mice. Accordingly, injection of more differentiated monolayer cells derived from spheres results in significantly decelerated tumor growth. For our study, two breast cancer cell lines were generated from primary tumors and cultured as mammospheres or as their adherent counterparts. We examined the in vivo tumorigenicity of these cells by injecting serial dilutions into immunodeficient mice. Inoculation of 106 cells per mouse led to rapid tumor formation, irrespective of cell line or culture conditions. However, after injection of only 103 cells, solely sphere cells were highly tumorigenic. In vitro, we investigated differentiation markers, established breast CSC markers and conducted mRNA profiling. Cytokeratin 5 and 18 were increased in both monolayer cell types, indicating a more differentiated phenotype. All cell lines were CD24-/CD44+ and did not express CD133, CD326 or E-cadherin. ALDH1 activity was not detectable in any cell line. A verapamil‑sensitive Hoechst side population was present in sphere cells, but there was no correlation with tumorigenicity in vivo. mRNA profiling did not reveal upregulation of relevant transcription factors. In vitro cell cycle kinetics and in vivo tumor doubling times displayed no difference between sphere and monolayer cultures. Our data indicate that intrinsic genetic and functional markers investigated are not indicative of the in vivo tumori-genicity of putative breast tumor-initiating cells.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

View References

1. 

LD WoodDW ParsonsS JonesThe genomic landscapes of human breast and colorectal cancersScience31811081113200710.1126/science.114572017932254

2. 

J StinglC CaldasMolecular heterogeneity of breast carcinomas and the cancer stem cell hypothesisNat Rev Cancer7791799200710.1038/nrc221217851544

3. 

L VermeulenMR SprickK KemperG StassiJP MedemaCancer stem cells - old concepts, new insightsCell Death Differ15947958200810.1038/cdd.2008.2018259194

4. 

K PolyakRA WeinbergTransitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traitsNat Rev Cancer9265273200910.1038/nrc262019262571

5. 

RP HillIdentifying cancer stem cells in solid tumors: case not provenCancer Res6618911895200610.1158/0008-5472.CAN-05-345016488984

6. 

M ShipitsinK PolyakThe cancer stem cell hypothesis: in search of definitions, markers, and relevanceLab Invest88459463200810.1038/labinvest.2008.1418379567

7. 

RW ChoMF ClarkeRecent advances in cancer stem cellsCurr Opin Genet Dev184853200810.1016/j.gde.2008.01.017

8. 

K PolyakBreast cancer stem cells: a case of mistaken identity?Stem Cell Rev3107109200710.1007/s12015-007-0020-817873341

9. 

JC LawsonGL BlatchAL EdkinsCancer stem cells in breast cancer and metastasisBreast Cancer Res Treat118241254200910.1007/s10549-009-0524-919731012

10. 

M Al-HajjMS WichaA Benito-HernandezSJ MorrisonMF ClarkeProspective identification of tumorigenic breast cancer cellsProc Natl Acad Sci USA10039833988200310.1073/pnas.053029110012629218

11. 

MJ GrimshawL CooperK PapazisisMammosphere culture of metastatic breast cancer cells enriches for tumorigenic breast cancer cellsBreast Cancer Res10R52200810.1186/bcr210618541018

12. 

M ShipitsinLL CampbellP ArganiMolecular definition of breast tumor heterogeneityCancer Cell11259273200710.1016/j.ccr.2007.01.01317349583

13. 

SY ParkM GönenHJ KimF MichorK PolyakCellular and genetic diversity in the progression of in situ human breast carcinomas to an invasive phenotypeJ Clin Invest120636644201010.1172/JCI4072420101094

14. 

MJ MeyerJM FlemingMA AliMW PeseskyE GinsburgBK VonderhaarDynamic regulation of CD24 and the invasive, CD44pos CD24neg phenotype in breast cancer cell linesBreast Cancer Res11R82200910.1186/bcr244919906290

15. 

F ReimY DombrowskiC RitterImmunoselection of breast and ovarian cancer cells with trastuzumab and natural killer cells: selective escape of CD44high/CD24low/HER2low breast cancer stem cellsCancer Res6980588066200910.1158/0008-5472.CAN-09-0834

16. 

H TanakaM NakamuraC KamedaThe Hedgehog signaling pathway plays an essential role in maintaining the CD44+CD24−/low subpopulation and the side population of breast cancer cellsAnticancer Res2921472157200919528475

17. 

CJ CreightonX LiM LandisResidual breast cancers after conventional therapy display mesenchymal as well as tumor-initiating featuresProc Natl Acad Sci USA1061382013825200910.1073/pnas.0905718106

18. 

S AulmannN WaldburgerR PenzelM AndrulisP SchirmacherHP SinnReduction of CD44(+)/CD24(−) breast cancer cells by conventional cytotoxic chemotherapyHum Pathol415745812010

19. 

C GinestierMH HurE Charafe-JauffretALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcomeCell Stem Cell1555567200710.1016/j.stem.2007.08.01418371393

20. 

E Charafe-JauffretC GinestierF IovinoBreast cancer cell lines contain functional cancer stem cells with metastatic capacity and a distinct molecular signatureCancer Res6913021313200910.1158/0008-5472.CAN-08-274119190339

21. 

E Charafe-JauffretC GinestierF IovinoAldehyde dehydrogenase 1-positive cancer stem cells mediate metastasis and poor clinical outcome in inflammatory breast cancerClin Cancer Res164555201010.1158/1078-0432.CCR-09-163020028757

22. 

JS HanDL CroweTumor initiating cancer stem cells from human breast cancer cell linesInt J Oncol3414491453200919360358

23. 

G OuyangZ WangX FangJ LiuCJ YangMolecular signaling of the epithelial to mesenchymal transition in generating and maintaining cancer stem cellsCell Mol Life Sci6726052618201010.1007/s00018-010-0338-220238234

24. 

F VesunaA LisokB KimbleV RamanTwist modulates breast cancer stem cells by transcriptional regulation of CD24 expressionNeoplasia1113181328200920019840

25. 

SA ManiW GuoMJ LiaoThe epithelial-mesenchymal transition generates cells with properties of stem cellsCell133704715200810.1016/j.cell.2008.03.02718485877

26. 

G DontuWM AbdallahJM FoleyIn vitro propagation and transcriptional profiling of human mammary stem/progenitor cellsGenes Dev1712531270200310.1101/gad.106180312756227

27. 

D PontiA CostaN ZaffaroniIsolation and in vitro propagation of tumorigenic breast cancer cells with stem/progenitor cell propertiesCancer Res6555065511200510.1158/0008-5472.CAN-05-062615994920

28. 

A IvascuM KubbiesDiversity of cell-mediated adhesions in breast cancer spheroidsInt J Oncol3114031413200717982667

29. 

A IvascuM KubbiesRapid generation of single-tumor spheroids for high-throughput cell function and toxicity analysisJ Biomol Screen11922932200610.1177/108705710629276316973921

30. 

E LimF VaillantD WuAberrant luminal progenitors as the candidate target population for basal tumor development in BRCA1 mutation carriersNat Med15907915200910.1038/nm.200019648928

31. 

C StueltenSD MertinsIJ BuschComplex display of putative tumor stem cell markers in the NCI60 tumor cell line panelStem Cells28649660201010.1002/stem.32420178109

32. 

V NeumeisterS AgarwalJ BordeauxRL CampDL RimmIn situ identification of putative cancer stem cells by multiplexing ALDH1, CD44, and cytokeratin identifies breast cancer patients with poor prognosisAm J Pathol17621312138201010.2353/ajpath.2010.09071220228222

33. 

GV GlinskyO BerezovskaAB GlinskiiMicroarray analysis identifies a death-from-cancer signature predicting therapy failure in patients with multiple types of cancerJ Clin Invest11515031521200510.1172/JCI2341215931389

34. 

A BergamaschiYH KimKA KweiCAMK1D amplification implicated in epithelial-mesenchymal transition in basal-like breast cancerMol Oncol2327239200810.1016/j.molonc.2008.09.00419383354

35. 

N KotajaP Sassone-CorsiPlzf pushes stem cellsNat Genet36551553200410.1038/ng0604-55115167928

36. 

JT DeAngelisY LiN MitchellL WilsonH KimTO Tollefsbol2D difference gel electrophoresis analysis of different time points during the course of neoplastic transformation of human mammary epithelial cellsJ Proteom Res10447458201110.1021/pr100533k

37. 

JC MartinBS HerbertBA HocevarDisabled-2 down-regulation promotes epithelial-to-mesenchymal transitionBr J Cancer10317161723201010.1038/sj.bjc.660597521063401

38. 

UG SathyanarayanaA PadarCX HuangAbberant promoter methylation and silencing of laminin-5-encoding genes in breast carcinomaClin Cancer Res963896394200314695139

39. 

D PontiN ZaffaroniC CapelliMG DiadoneBreast cancer stem cells: an overviewEur J Cancer4212191224200610.1016/j.ejca.2006.01.03116624548

40. 

M HuK PolyakMicroenvironmental regulation of cancer developmentCurr Opin Genet Dev182734200810.1016/j.gde.2007.12.006

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Lehmann C, Jobs G, Thomas M, Burtscher H and Kubbies M: Established breast cancer stem cell markers do not correlate with in vivo tumorigenicity of tumor-initiating cells. Int J Oncol 41: 1932-1942, 2012.
APA
Lehmann, C., Jobs, G., Thomas, M., Burtscher, H., & Kubbies, M. (2012). Established breast cancer stem cell markers do not correlate with in vivo tumorigenicity of tumor-initiating cells. International Journal of Oncology, 41, 1932-1942. https://doi.org/10.3892/ijo.2012.1654
MLA
Lehmann, C., Jobs, G., Thomas, M., Burtscher, H., Kubbies, M."Established breast cancer stem cell markers do not correlate with in vivo tumorigenicity of tumor-initiating cells". International Journal of Oncology 41.6 (2012): 1932-1942.
Chicago
Lehmann, C., Jobs, G., Thomas, M., Burtscher, H., Kubbies, M."Established breast cancer stem cell markers do not correlate with in vivo tumorigenicity of tumor-initiating cells". International Journal of Oncology 41, no. 6 (2012): 1932-1942. https://doi.org/10.3892/ijo.2012.1654
Copy and paste a formatted citation
x
Spandidos Publications style
Lehmann C, Jobs G, Thomas M, Burtscher H and Kubbies M: Established breast cancer stem cell markers do not correlate with in vivo tumorigenicity of tumor-initiating cells. Int J Oncol 41: 1932-1942, 2012.
APA
Lehmann, C., Jobs, G., Thomas, M., Burtscher, H., & Kubbies, M. (2012). Established breast cancer stem cell markers do not correlate with in vivo tumorigenicity of tumor-initiating cells. International Journal of Oncology, 41, 1932-1942. https://doi.org/10.3892/ijo.2012.1654
MLA
Lehmann, C., Jobs, G., Thomas, M., Burtscher, H., Kubbies, M."Established breast cancer stem cell markers do not correlate with in vivo tumorigenicity of tumor-initiating cells". International Journal of Oncology 41.6 (2012): 1932-1942.
Chicago
Lehmann, C., Jobs, G., Thomas, M., Burtscher, H., Kubbies, M."Established breast cancer stem cell markers do not correlate with in vivo tumorigenicity of tumor-initiating cells". International Journal of Oncology 41, no. 6 (2012): 1932-1942. https://doi.org/10.3892/ijo.2012.1654
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team