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Characterization of hybrid cells derived from spontaneous fusion events between breast epithelial cells exhibiting stem-like characteristics and breast cancer cells

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Abstract

Several data of the past years clearly indicated that the fusion of tumor cells and tumor cells or tumor cells and normal cells can give rise to hybrids cells exhibited novel properties such as an increased malignancy, drug resistance, or resistance to apoptosis. In the present study we characterized hybrid cells derived from spontaneous fusion events between the breast epithelial cell line M13SV1-EGFP-Neo and two breast cancer cell lines: HS578T-Hyg and MDA-MB-435-Hyg. Short-tandem-repeat analysis revealed an overlap of parental alleles in all hybrid cells indicating that hybrid cells originated from real cell fusion events. RealTime-PCR-array gene expression data provided evidence that each hybrid cell clone exhibited a unique gene expression pattern, resulting in a specific resistance of hybrid clones towards chemotherapeutic drugs, such as doxorubicin and paclitaxel, as well as a specific migratory behavior of hybrid clones towards EGF. For instance, M13MDA435-4 hybrids showed a marked resistance towards etoposide, doxorubicin and paclitaxel, whereas hybrid clones M13MDA-435-1 and -2 were only resistant towards etoposide. Likewise, all investigated M13MDA435 hybrids responded to EGF with an increased migratory activity, whereas the migration of parental MDA-MB-435-Hyg cells was blocked by EGF, suggesting that M13MDA435 hybrids may have acquired a new motility pathway. Similar findings have been obtained for M13HS hybrids. We conclude from our data that they further support the hypothesis that cell fusion could give rise to drug resistant and migratory active tumor (hybrid) cells in cancer.

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Acknowledgments

The authors are grateful to the technical assistance of Silvia Keil. This work was supported by the Verein zur Förderung der Krebsforschung e.V., Heidelberg, Germany and the Fritz-Bender-Foundation, Munich, Germany.

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Authors and Affiliations

  1. Institute of Immunology, Zentrum für Biomedizinische Ausbildung und Forschung an der UWH (ZBAF), Witten/Herdecke University, Stockumer Str. 10, 58448, Witten, Germany

    Thomas Dittmar, Sonja Haverkampf, Georg Reith, Bernd Niggemann & Kurt S. Zänker

  2. 2nd Department of Medicine, Klinikum rechts der Isar, Technical University of Munich, Ismaninger Strasse 22, 81675, Munich, Germany

    Sarah Schwitalla

  3. Medizinische Klinik II m.S. Hämatologie/Onkologie, Charité, Campus Mitte, 10117, Berlin, Germany

    Jeanette Seidel

  4. Department of Tumor Biology, University Hospital Hamburg-Eppendorf, Campus Forschung N27, Martinistr. 52, 20246, Hamburg, Germany

    Sönke Meyer-Staeckling & Burkhard H. Brandt

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  1. Thomas Dittmar
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  2. Sarah Schwitalla
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Correspondence to Thomas Dittmar.

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Dittmar, T., Schwitalla, S., Seidel, J. et al. Characterization of hybrid cells derived from spontaneous fusion events between breast epithelial cells exhibiting stem-like characteristics and breast cancer cells. Clin Exp Metastasis 28, 75–90 (2011). https://doi.org/10.1007/s10585-010-9359-3

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  • DOI: https://doi.org/10.1007/s10585-010-9359-3

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