title: Evaluating the role of substance P in the growth of brain tumors.
abstract: Recent research has investigated the expression and secretion of neuropeptides by tumors, and the potential of these peptides to facilitate tumor growth and spread. In particular, substance P (SP) and its receptor NK1 have been implicated in tumor cell growth and evasion of apoptosis, although few studies have examined this relationship in vivo. The present study used both in vitro and in vivo models to characterize the role of SP in tumor pathogenesis. Immunohistochemical assessment of human primary and secondary brain tumor tissue demonstrated a marked increase in SP and its NK1 receptor in all tumor types investigated. Of the metastatic tumors, melanoma demonstrated particularly elevated SP and NK1 receptor staining. Subsequently, A-375 human melanoma cell line was examined in vitro and found to express both SP and the NK1 receptor. Treatment with the NK1 receptor antagonist Emend IV resulted in decreased cell viability and an increase in cell death in this cell line in vitro. An animal model of brain tumors using the same cell line was employed to assess the effect of Emend IV on tumor growth in vivo. Administration of Emend IV was found to decrease tumor volume and decrease cellular proliferation indicating that SP may play a role in tumor pathogenesis within the brain. We conclude that SP may provide a novel therapeutic target in the treatment of certain types of brain tumors, with further research required to determine whether the role of SP in cancer is tumor-type dependent.
authors.affiliation: Adelaide Centre for Neuroscience Research and Discipline of Anatomy and Pathology, University of Adelaide, Adelaide, South Australia, Australia. Electronic address: Elizabeth.harfordwright@adelaide.edu.au.
authors.forename: E
authors.initials: E
authors.lastname: Harford-Wright
authors.affiliation: Adelaide Centre for Neuroscience Research and Discipline of Anatomy and Pathology, University of Adelaide, Adelaide, South Australia, Australia. Electronic address: kate.m.lewis@adelaide.edu.au.
authors.forename: K M
authors.initials: KM
authors.lastname: Lewis
authors.affiliation: Adelaide Centre for Neuroscience Research and Discipline of Anatomy and Pathology, University of Adelaide, Adelaide, South Australia, Australia. Electronic address: Robert.vink@adelaide.edu.au.
authors.forename: R
authors.initials: R
authors.lastname: Vink
authors.affiliation: Adelaide Centre for Neuroscience Research and Discipline of Anatomy and Pathology, University of Adelaide, Adelaide, South Australia, Australia. Electronic address: mounir.ghabriel@adelaide.edu.au.
authors.forename: M N
authors.initials: MN
authors.lastname: Ghabriel
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D064729:Neurokinin-1 Receptor Antagonists / Q000494:pharmacology; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D064729:Neurokinin-1 Receptor Antagonists; D018040:Receptors, Neurokinin-1; D013373:Substance P
keywords: NK1 antagonist; brain tumors; cancer therapy; neuropeptides; substance P