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.