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The neuronal guidance cue Slit2 induces targeted migration and may play a role in brain metastasis of breast cancer cells

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Abstract

Cell migration is essential in many diverse processes ranging from embryonic development to wound healing and immune response. Cancer cells have recently been shown to utilize chemoattraction mechanisms mediated by chemokines and their respective receptors, e.g., the CXCL12/CXCR4 pathway normally found in leukocytes. Here we show that Slit2, a secreted protein signaling through the Roundabout (Robo) receptor as a chemorepellent in axon guidance and neuronal migration, acts as a potent chemoattractant for breast cancer cells. Comparing cell lines specifically metastasizing to either brain or bone, we found significant differences in their responses to CXCL12 and Slit2 treatments, suggesting a role for Slit/Robo signaling in brain metastasis.

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Abbreviations

MMP9:

Matrix metalloprotease 9

VEGF:

Vascular endothelial growth factor

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Acknowledgements

This work was supported by “Medizinisch-wissenschaftlicher Fonds des Bürgermeisters der Bundeshauptstadt Wien”, Project No. 2185,

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Author notes

  1. Günther A. Rezniczek

    Present address: Department of Molecular Cell Biology, Max F. Perutz Laboratories, University of Vienna, Vienna, Austria

Authors and Affiliations

  1. Division of Gynecology, Molecular Oncology Group, Department of Obstetrics and Gynecology, Medical University of Vienna, Währinger Gürtel 18–20, EBO 05Q, 1090, Vienna, Austria

    Bernd C. Schmid, Günther A. Rezniczek, Gerhild Fabjani, Sepp Leodolter & Robert Zeillinger

  2. Ludwig-Boltzmann Institute for Gynecological Oncology and Reproductive Medicine, Vienna, Austria

    Gerhild Fabjani & Sepp Leodolter

  3. Division of Endocrinology and Metabolism, Department of Medicine, University of Texas Health Science Center, San Antonio, TX, USA

    Toshiyuki Yoneda

Authors
  1. Bernd C. Schmid
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  2. Günther A. Rezniczek
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  3. Gerhild Fabjani
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  4. Toshiyuki Yoneda
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  5. Sepp Leodolter
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  6. Robert Zeillinger
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Corresponding author

Correspondence to Robert Zeillinger.

Additional information

Bernd C. Schmid and Günther A. Rezniczek contributed equally to this work.

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Schmid, B.C., Rezniczek, G.A., Fabjani, G. et al. The neuronal guidance cue Slit2 induces targeted migration and may play a role in brain metastasis of breast cancer cells. Breast Cancer Res Treat 106, 333–342 (2007). https://doi.org/10.1007/s10549-007-9504-0

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  • DOI: https://doi.org/10.1007/s10549-007-9504-0

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