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Human mesenchymal stem cells induce E-cadherin degradation in breast carcinoma spheroids by activating ADAM10

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Abstract

Mesenchymal stem cells (MSCs) have been shown to communicate with tumor cells. We analyzed the effect of human MSCs (hMSCs) on breast cancer cells in three-dimensional cultures. By using GFP expression and immunohistochemistry, we show that hMSCs invade 3D breast cancer cell aggregates. hMSCs caused breast cancer spheroids to become disorganized which was accompanied by a disruption of cell–cell adhesion, E-cadherin cleavage, and nuclear translocation of E-cadherin, but not by epithelial/mesenchymal transition or by an increase in ERK1/2 activity. In addition, hMSCs enhanced the motility of breast cancer cells. Inhibition of ADAM10 (a disintegrin and metalloprotease 10), known to cleave E-cadherin, prevented both hMSC-mediated E-cadherin cleavage and enhanced migration. Our data suggest that hMSCs interfere with cell–cell adhesion and enhance migration of breast cancer cells by activating ADAM10.

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Acknowledgments

We thank GlaxoSmithKline for kindly providing us with GI254023X, and Stephan Reshkin for critically reading the manuscript. This work was supported by grant FKZ SI/08 provided by Land Sachsen-Anhalt (Germany).

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Authors and Affiliations

  1. Klinik für Gynäkologie, Universität Halle, Halle (Saale), Germany

    Angela Dittmer, Kristina Hohlfeld & Jürgen Dittmer

  2. Zentrum für Innere Medizin, Klinik für Innere Medizin IV, Universität Halle, Halle (Saale), Germany

    Jana Lützkendorf & Lutz P. Müller

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  1. Angela Dittmer
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Correspondence to Jürgen Dittmer.

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Dittmer, A., Hohlfeld, K., Lützkendorf, J. et al. Human mesenchymal stem cells induce E-cadherin degradation in breast carcinoma spheroids by activating ADAM10. Cell. Mol. Life Sci. 66, 3053–3065 (2009). https://doi.org/10.1007/s00018-009-0089-0

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