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Neurokinin‐1 receptor expression and antagonism by the NK‐1R antagonist maropitant in canine melanoma cell lines and primary tumour tissues
Author(s) -
Borrego J. F.,
Huelsmeyer M. K.,
Pinkerton M. E.,
Muszynski J. L.,
Miller S. A. K.,
Kurzman I. D.,
Vail D. M.
Publication year - 2016
Publication title -
veterinary and comparative oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.864
H-Index - 34
eISSN - 1476-5829
pISSN - 1476-5810
DOI - 10.1111/vco.12093
Subject(s) - in vivo , cell culture , cancer research , messenger rna , immunohistochemistry , tachykinin receptor 1 , apoptosis , melanoma , in vitro , receptor , substance p , medicine , biology , pathology , gene , neuropeptide , biochemistry , genetics , microbiology and biotechnology
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.