Neurokinin-1 receptor expression and antagonism by the NK-1R antagonist maropitant in canine melanoma cell lines and primary tumour tissues

Authors

  • J. F. Borrego,

    1. The Barbara Suran Comparative Oncology Research Institute, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA
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    • Present address: Instituto Veterinario de Oncología Comparada, IVOC, Valencia, Spain
  • M. K. Huelsmeyer,

    1. The Barbara Suran Comparative Oncology Research Institute, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA
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  • M. E. Pinkerton,

    1. The Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA
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  • J. L. Muszynski,

    1. The Barbara Suran Comparative Oncology Research Institute, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA
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  • S. A. K. Miller,

    1. The Barbara Suran Comparative Oncology Research Institute, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA
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  • I. D. Kurzman,

    1. The Barbara Suran Comparative Oncology Research Institute, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA
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  • D. M. Vail

    Corresponding author
    1. The Barbara Suran Comparative Oncology Research Institute, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA
    2. Carbone Comprehensive Cancer Center, University of Wisconsin-Madison, Madison, WI, USA
    • Correspondence address:

      D. M. Vail

      The Barbara Suran Comparative Oncology Research Institute, School of Veterinary Medicine

      University of Wisconsin-Madison

      2015 Linden Drive

      Madison

      WI 53706, USA

      e-mail: vaild@svm.vetmed.wisc.edu

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  • Presented in part in abstract form at the 2011 annual meetings of the Veterinary Cancer Society (Albuquerque, NM) and the European Society of Veterinary Oncology (Glasgow, UK).

Abstract

We interrogated the neurokinin-1 receptor (NK-1R)/substance P (SP) pathway in canine melanoma tumour tissues and cell lines. NK-1R messenger RNA (mRNA) and protein expression were observed in the majority of tumour tissues. Immunohistochemical assessment of archived tissue sections revealed NK-1R immunoreactivity in 11 of 15 tumours, which may have diagnostic, prognostic and therapeutic utility. However, we were unable to identify a preclinical in vitro cell line or in vivo xenograft model that recapitulates NK-1R mRNA and protein expression documented in primary tumours. While maropitant inhibited proliferation and enhanced apoptosis in cell lines, in the absence of documented NK-1R expression, this may represent off-target effects. Furthermore, maropitant failed to suppress tumour growth in a canine mouse xenograft model derived from a cell line expressing mRNA but not protein. While NK-1R represents a novel target, in the absence of preclinical models, in-species clinical trials will be necessary to investigate the therapeutic potential for antagonists such as maropitant.

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