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
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  • Published online on: October 5, 2012     https://doi.org/10.3892/ijo.2012.1654
  • Pages: 1932-1942
  • Copyright: © Lehmann et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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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.
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December 2012
Volume 41 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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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