Substance P activates responses correlated with tumour growth in human glioma cell lines bearing tachykinin NK1 receptors

被引:72
作者
Palma, C
Nardelli, F
Manzini, S
Maggi, CA
机构
[1] Menarini Ric, Dept Pharmacol, I-00040 Pomezia, RM, Italy
[2] Menarini Ric, I-50131 Florence, Italy
关键词
glioma; substance P; tachykinin NK1 receptor; cytokine production; proliferation;
D O I
10.1038/sj.bjc.6690039
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The neuropeptide substance P (SP), by stimulating tachykinin NK1 receptors (NK1R), 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 NK1R 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 NK1R+ 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 NK1R+, but not of NK1R- glioma cell lines. Also, NKA stimulated the proliferation and cytokine secretion in NK1R+ glioma cell lines. All the stimulant effects of SP/NKA on NK1R+ glioma cell lines were completely blocked by a specific tachykinin NK1R antagonist, MEN 11467. These data support the potential use of tachykinin NK1R antagonist for controlling the proliferative rate of human gliomas.
引用
收藏
页码:236 / 243
页数:8
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