Evaluating the role of substance P in the growth of brain tumors

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• 作者：E. Harford-Wright ; K.M. Lewis ; R. Vink ; M.N. Ghabriel
• 关键词：ATCC ; American-Type Culture Collection ; BSA ; bovine serum albumin ; CCM ; complete culture medium ; DAB ; 3 ; 3&prime ; -diaminobenzidine ; ELISA ; enzyme-linked immunosorbent assay ; GBM ; glioblastoma multiforme ; HRP ; horseradish peroxidase ; LDH ; lactate dehydrogenase ; NBF ; neutral-buffered formalin ; NHMRC ; National Health and Medical Research Council ; RAH ; Royal Adelaide Hospital ; SP ; substance P ; SPC ; streptavidin&ndash ; peroxidase conjugate ; TBS ; Tris-buffered saline ; TMB ; 3 ; 3&prime ; -5&prime ; 5&prime ; -te
• 刊名：Neuroscience
• 出版年：7 March, 2014
• 年：2014
• 卷：261
• 期：Complete
• 页码：85-94
• 全文大小：2467 K

文摘

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 m>in vivom>. The present study used both m>in vitrom> and m>in vivom> 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 m>in vitrom> 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 m>in vitrom>. An animal model of brain tumors using the same cell line was employed to assess the effect of Emend IV on tumor growth m>in vivom>. 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.