Notch signaling mediates melanoma–endothelial cell communication and melanoma cell migration

Authors

  • Jason D. Howard,

    1. The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
    2. Program in Pharmacology and Molecular Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
    3. Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
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  • Whei F. Moriarty,

    1. The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
    2. Program in Cellular and Molecular Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
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  • JinSeok Park,

    1. Department of Biomedical Engineering, Whitaker Institute for Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
    2. Institute for Cellular Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
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  • Katherine Riedy,

    1. Department of Dermatology, Boston University School of Medicine, Boston, MA, USA
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  • Izabela P. Panova,

    1. Department of Dermatology, Boston University School of Medicine, Boston, MA, USA
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  • Christine H. Chung,

    1. The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
    2. Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
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  • Kahp-Yang Suh,

    1. School of Mechanical and Aerospace Engineering, Seoul National University, Seoul, South Korea
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  • Andre Levchenko,

    1. Department of Biomedical Engineering, Whitaker Institute for Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
    2. Institute for Cellular Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
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  • Rhoda M. Alani

    Corresponding author
    1. Program in Pharmacology and Molecular Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
    2. Program in Cellular and Molecular Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
    3. Department of Dermatology, Boston University School of Medicine, Boston, MA, USA
    • The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
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CORRESPONDENCE Rhoda M. Alani, e-mail: alani@bu.edu

Summary

Stromal and cellular components within the tumor microenvironment significantly influence molecular signals mediating tumor growth and progression. We recently performed a screen to evaluate critical mediators of melanoma–endothelial communication and identified several molecular pathways associated with these cellular networks, including Notch3. Here, we evaluate the nature of melanoma–endothelial communication mediated by Notch3 and its functional significance. We find that Notch3 is specifically upregulated in melanoma–endothelial cell cocultures and is functionally associated with increased Notch signaling in melanoma cells. Furthermore, induced Notch3 signaling in melanoma cell lines leads to enhanced tumor cell migration without associated increases in tumor cell growth. Additionally, Notch3 expression is specifically associated with malignant patient samples and is not evident in benign nevi. We conclude that Notch3 mediates melanoma–endothelial cell communication and tumor cell migration and may serve as a meaningful therapeutic target for this aggressive malignancy.

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