Substance P activates responses correlated with tumour growth in human glioma cell lines bearing tachykinin NK(1) receptors

The neuropeptide substance P (SP), by stimulating tachykinin NK(1)receptors (NK(1)R), triggers a number of biological responses in human glioma cells which are potentially relevant for tumour growth. First, radioligand binding studies demonstrated the presence of tachykinin NK(1)R on SNB-19, DBTRG-05 MG and U373 MG, but not on U138 MG and MOG-G-GCM human glioma cell lines. Second, application of SP or neurokinin A (NKA) to NK(1)R(+)glioma cell lines increased the secretion of interleukin 6 (IL-6) and potentiated IL-6 secretion induced by IL-1β. SP also up-regulated the release of transforming growth factor β1 (TGF-β1) by the U373 MG glioma cell line. Third, SP induced new DNA synthesis and enhanced the proliferation rate of NK(1)R(+), but not of NK(1)R(−)glioma cell lines. Also, NKA stimulated the proliferation and cytokine secretion in NK(1)R(+)glioma cell lines. All the stimulant effects of SP/NKA on NK(1)R(+)glioma cell lines were completely blocked by a specific tachykinin NK(1)R antagonist, MEN 11467. These data support the potential use of tachykinin NK(1)R antagonist for controlling the proliferative rate of human gliomas. © 1999 Cancer Research Campaign