title: Neurokinin-1 receptor expression and antagonism by the NK-1R antagonist maropitant in canine melanoma cell lines and primary tumour tissues.
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.
authors.affiliation: The Barbara Suran Comparative Oncology Research Institute, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: J F
authors.initials: JF
authors.lastname: Borrego
authors.affiliation: The Barbara Suran Comparative Oncology Research Institute, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: M K
authors.initials: MK
authors.lastname: Huelsmeyer
authors.affiliation: The Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Pinkerton
authors.affiliation: The Barbara Suran Comparative Oncology Research Institute, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Muszynski
authors.affiliation: The Barbara Suran Comparative Oncology Research Institute, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: S A K
authors.initials: SA
authors.lastname: Miller
authors.affiliation: The Barbara Suran Comparative Oncology Research Institute, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: I D
authors.initials: ID
authors.lastname: Kurzman
authors.affiliation: The Barbara Suran Comparative Oncology Research Institute, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA.|Carbone Comprehensive Cancer Center, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Vail
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004283:Dog Diseases; D004285:Dogs; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D008545:Melanoma / Q000662:veterinary*; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000378:metabolism; D064729:Neurokinin-1 Receptor Antagonists / Q000494:pharmacology; D011812:Quinuclidines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018040:Receptors, Neurokinin-1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D064729:Neurokinin-1 Receptor Antagonists; D011812:Quinuclidines; D012333:RNA, Messenger; D018040:Receptors, Neurokinin-1; C518176:maropitant
keywords: NK-1R; canine; maropitant; melanoma; substance P