SPHINGOSINE 1-PHOSPHATE, A SPECIFIC ENDOGENOUS SIGNALING MOLECULE CONTROLLING CELL MOTILITY AND TUMOR-CELL INVASIVENESS
SPHINGOSINE 1-PHOSPHATE, A SPECIFIC ENDOGENOUS SIGNALING MOLECULE CONTROLLING CELL MOTILITY AND TUMOR-CELL INVASIVENESS
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DOI：
10.1073/pnas.89.20.9686
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发表时间：
1992-10-15
影响因子：
11.1
通讯作者：
IGARASHI, Y
中科院分区：
文献类型：
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作者：
SADAHIRA, Y;RUAN, FQ;IGARASHI, Y
1-磷酸鞘氨醇(Sph-1-P)是Sph酶降解Sph的最初产物，在10-100 nM的浓度范围内对B16黑色素瘤和其他类型的细胞的运动和吞噬运动有很强的抑制作用。它还通过滤膜上厚厚的一层Matrigel抑制肿瘤细胞的“化学侵袭”。这种抑制作用由Sph、Sph的N-甲基衍生物或其他相关的鞘磷脂和磷脂产生，或根本不产生。SPH-1-P不抑制细胞增殖或蛋白激酶C(PKC)活性，而SPH和N-甲基SPH一般抑制PKC活性和细胞生长。放射性标记的[H-3]sph和[C-14]N-甲基-sph被迅速整合到B16黑色素瘤细胞中。然而，[C-14]N-甲基-Sph没有被代谢转化为其他化合物，而[H-3]Sph在10分钟内被有效地转化为Sph-1-P，然后转化为其他鞘磷脂和磷脂。Sph-1-P对细胞运动和肿瘤细胞侵袭的抑制作用可能是一种独立于PKC和其他已知跨膜信号机制的特殊现象，基于未知的机制。它可能直接影响肌动蛋白细丝的组织组装。由于外源Sph能迅速转化为Sph-1-P，已报道的Sph的某些效应可能归因于这种转化。
Sphingosine 1-phosphate (Sph-1-P), the initial product of Sph degradation by Sph kinase, was shown to be a strong inhibitor of cell motility and phagokinesis of B16 melanoma and other types of cells at 10-100 nM concentration. It also inhibited "chemoinvasion' of tumor cells through a thick layer of Matrigel on a filter membrane. Such inhibitory effects were produced minimally or not at all by Sph, N-methyl derivatives of Sph, or other related sphingolipids and phospholipids. Sph-1-P did not inhibit cell proliferation or protein kinase C (PKC) activity, in contrast to Sph and N-methyl-Sph, which inhibit PKC activity and cell growth in general. Radiolabeled [H-3]Sph and [C-14]N-methyl-Sph were rapidly incorporated into B16 melanoma cells. However, [C-14]N-methyl-Sph was not metabolically converted into other compounds, whereas [H-3]Sph was efficiently converted within 10 min to Sph-1-P, followed by conversion to other sphingolipids and phospholipids. The inhibitory effect of Sph-1-P on cell motility and tumor cell invasiveness could be a specific phenomenon independent of PKC and other known transmembrane signaling mechanisms, based on an unknown mechanism. It may directly affect organizational assembly of actin filaments. Since exogenous Sph is rapidly converted into Sph-1-P, some reported effects of Sph may be ascribable to such conversion.