SPHINGOSINE 1-PHOSPHATE, A SPECIFIC ENDOGENOUS SIGNALING MOLECULE CONTROLLING CELL MOTILITY AND TUMOR-CELL INVASIVENESS

被引:240
作者
SADAHIRA, Y [1 ]
RUAN, FQ [1 ]
HAKOMORI, SI [1 ]
IGARASHI, Y [1 ]
机构
[1] UNIV WASHINGTON,DEPT PATHOBIOL,SEATTLE,WA 98195
关键词
D O I
10.1073/pnas.89.20.9686
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:9686 / 9690
页数:5
相关论文
共 32 条
  • [1] ALBINI A, 1987, CANCER RES, V47, P3239
  • [2] PHAGOKINETIC TRACKS OF 3T3-CELLS
    ALBRECHTBUEHLER, G
    [J]. CELL, 1977, 11 (02) : 395 - 404
  • [4] BLIGH EG, 1959, CAN J BIOCHEM PHYS, V37, P911
  • [5] MEMBRANE CYTOSKELETON INTERACTIONS IN ANIMAL-CELLS
    CARRAWAY, KL
    CARRAWAY, CAC
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA, 1989, 988 (02) : 147 - 171
  • [6] PRESENCE OF AN SH2 DOMAIN IN THE ACTIN-BINDING PROTEIN TENSIN
    DAVIS, S
    LU, ML
    LO, SH
    LIN, S
    BUTLER, JA
    DRUKER, BJ
    ROBERTS, TM
    AN, Q
    CHEN, LB
    [J]. SCIENCE, 1991, 252 (5006) : 712 - 715
  • [7] ENDO K, 1991, CANCER RES, V51, P1613
  • [8] A CERAMIDE ANALOG INHIBITS T-CELL PROLIFERATIVE RESPONSE THROUGH INHIBITION OF GLYCOSPHINGOLIPID SYNTHESIS AND ENHANCEMENT OF N,N-DIMETHYLSPHINGOSINE SYNTHESIS
    FELDINGHABERMANN, B
    IGARASHI, Y
    FENDERSON, BA
    PARK, LS
    RADIN, NS
    INOKUCHI, J
    STRASSMANN, G
    HANDA, K
    HAKOMORI, S
    [J]. BIOCHEMISTRY, 1990, 29 (26) : 6314 - 6322
  • [9] INTRACELLULAR CALCIUM RELEASE MEDIATED BY SPHINGOSINE DERIVATIVES GENERATED IN CELLS
    GHOSH, TK
    BIAN, J
    GILL, DL
    [J]. SCIENCE, 1990, 248 (4963) : 1653 - 1656
  • [10] CAPNOCYTOPHAGA SPP CONTAIN SULFONOLIPIDS THAT ARE NOVEL IN PROCARYOTES
    GODCHAUX, W
    LEADBETTER, ER
    [J]. JOURNAL OF BACTERIOLOGY, 1980, 144 (02) : 592 - 602