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PMID: 7881110 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Review

Sphingosine-1-phosphate, a novel second messenger involved in cell growth regulation and signal transduction, affects growth and invasiveness of human breast cancer cells.

Breast cancer research and treatment ·Vol. 31 ·No. 2-3 ·1994-00-00 ·Pages 337-48

Spiegel S, Olivera A, Zhang H, Thompson EW, Su Y, Berger A

Abstract

This review will focus on the role of sphingosine and its phosphorylated derivative sphingosine-1-phosphate (SPP) in cell growth regulation and signal transduction. We will show that many of the effects attributed to sphingosine in quiescent Swiss 3T3 fibroblasts are mediated via its conversion to SPP. We propose that SPP has appropriate properties to function as an intracellular second messenger based on the following: it elicits diverse cellular responses; it is rapidly produced from sphingosine by a specific kinase and rapidly degraded by a specific lyase; its concentration is low in quiescent cells but increases rapidly and transiently in response to the growth factors, fetal calf serum (FCS) and platelet derived growth factor (PDGF); it releases Ca2+ from internal sources in an InsP3-independent manner; and finally, it may link sphingolipid signaling pathways to cellular ras-mediated signaling pathways by elevating phosphatidic acid levels. The effects of this novel second messenger on growth, differentiation and invasion of human breast cancer cells will be discussed.

MeSH Terms
3T3 Cells Animals Blood Physiological Phenomena Breast Neoplasms/chemistry,pathology Calcium/metabolism Cattle Cell Division/drug effects Cell Movement Growth Substances/physiology Humans Lysophospholipids Mice Models, Biological Neoplasm Invasiveness/physiopathology Phosphatidic Acids/pharmacology Platelet-Derived Growth Factor/pharmacology Second Messenger Systems Signal Transduction Sphingosine/analogs & derivatives,metabolism Tumor Cells, Cultured
Chemicals
Growth Substances Lysophospholipids Phosphatidic Acids Platelet-Derived Growth Factor sphingosine 1-phosphate Sphingosine Calcium
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Spiegel S
Department of Biochemistry and Molecular Biology, Georgetown University Medical Center, Washington, DC 20007.
Olivera A
Zhang H
Thompson E W
Su Y
Berger A
References (72)
72 references, click to expand
  1. Signal transduction by the platelet-derived growth factor receptor.
    Science. 1989 Mar 24;243(4898):1564-70 PMID: 2538922
  2. Functions of sphingolipids and sphingolipid breakdown products in cellular regulation.
    Science. 1989 Jan 27;243(4890):500-7 PMID: 2643164
  3. Signaling pathways for sphingosylphosphorylcholine-mediated mitogenesis in Swiss 3T3 fibroblasts.
    J Cell Biol. 1993 Jun;121(6):1385-95 PMID: 8389770
  4. Possible involvement of a GTP-binding protein, the substrate of islet-activating protein, in receptor-mediated signaling responsible for cell proliferation.
    J Biol Chem. 1987 Sep 15;262(26):12463-7 PMID: 3040750
  5. Phospholipids containing polyunsaturated fatty acyl groups are mitogenic for normal mouse mammary epithelial cells in serum-free primary cell culture.
    Proc Natl Acad Sci U S A. 1989 Jun;86(11):4122-6 PMID: 2471196
  6. Properties and specificities of sphingosine kinase from blood platelets.
    Hoppe Seylers Z Physiol Chem. 1973 Oct-Nov;354(10-11):1311-6 PMID: 4373363
  7. Modulation of the free sphingosine levels in human neutrophils by phorbol esters and other factors.
    J Biol Chem. 1988 Jul 5;263(19):9304-9 PMID: 3132460
  8. Cell regulation by sphingosine and more complex sphingolipids.
    J Bioenerg Biomembr. 1991 Feb;23(1):83-104 PMID: 2010436
  9. Inhibition of phosphatidic acid phosphohydrolase activity by sphingosine. Dual action of sphingosine in diacylglycerol signal termination.
    FEBS Lett. 1990 Dec 17;277(1-2):7-10 PMID: 2269371
  10. Role of ceramide as a lipid mediator of 1 alpha,25-dihydroxyvitamin D3-induced HL-60 cell differentiation.
    J Biol Chem. 1990 Sep 15;265(26):15823-31 PMID: 2394750
  11. Phosphatidic acid that accumulates in platelet-derived growth factor-stimulated Balb/c 3T3 cells is a potential mitogenic signal.
    J Biol Chem. 1992 Jun 5;267(16):10988-93 PMID: 1597441
  12. Inhibition of sphingosine kinase in vitro and in platelets. Implications for signal transduction pathways.
    J Biol Chem. 1992 Feb 15;267(5):3154-9 PMID: 1310683
  13. Sphingosine-1-phosphate as second messenger in cell proliferation induced by PDGF and FCS mitogens.
    Nature. 1993 Oct 7;365(6446):557-60 PMID: 8413613
  14. A cytoplasmic protein inhibits the GTPase activity of H-Ras in a phospholipid-dependent manner.
    Science. 1990 Nov 16;250(4983):982-5 PMID: 2237442
  15. Point mutation of an FGF receptor abolishes phosphatidylinositol turnover and Ca2+ flux but not mitogenesis.
    Nature. 1992 Aug 20;358(6388):678-81 PMID: 1379697
  16. The effect of GTPase activating protein upon ras is inhibited by mitogenically responsive lipids.
    Science. 1989 Jan 27;243(4890):522-6 PMID: 2536192
  17. Signaling through phosphatidylcholine breakdown.
    J Biol Chem. 1990 Jan 5;265(1):1-4 PMID: 2104616
  18. Effect of phospholipase C-gamma overexpression on PDGF-induced second messengers and mitogenesis.
    Science. 1990 May 4;248(4955):607-10 PMID: 2333512
  19. Regulation of breast cancer cells by hormones and growth factors: effects on proliferation and basement membrane invasiveness.
    Horm Res. 1989;32 Suppl 1:242-9 PMID: 2693328
  20. Lysosphingolipids inhibit protein kinase C: implications for the sphingolipidoses.
    Science. 1987 Feb 6;235(4789):670-4 PMID: 3101176
  21. Ceramide 1-phosphate, a novel phospholipid in human leukemia (HL-60) cells. Synthesis via ceramide from sphingomyelin.
    J Biol Chem. 1990 Sep 5;265(25):14917-21 PMID: 2394706
  22. A specific enhancing effect of N,N-dimethylsphingosine on epidermal growth factor receptor autophosphorylation. Demonstration of its endogenous occurrence (and the virtual absence of unsubstituted sphingosine) in human epidermoid carcinoma A431 cells.
    J Biol Chem. 1990 Apr 5;265(10):5385-9 PMID: 2318819
  23. Gangliosides as bimodal regulators of cell growth.
    Proc Natl Acad Sci U S A. 1987 Jan;84(1):141-5 PMID: 3540954
  24. Sphingosine-1-phosphate, a novel lipid, involved in cellular proliferation.
    J Cell Biol. 1991 Jul;114(1):155-67 PMID: 2050740
  25. Ca2+-mobilizing actions of platelet-derived growth factor differ from those of bombesin and vasopressin in Swiss 3T3 mouse cells.
    Proc Natl Acad Sci U S A. 1987 Aug;84(16):5768-72 PMID: 3039507
  26. Role of phospholipase D-derived diradylglycerol in the activation of the human neutrophil respiratory burst oxidase. Inhibition by phosphatidic acid phosphohydrolase inhibitors.
    J Immunol. 1992 Oct 15;149(8):2749-58 PMID: 1328385
  27. Differential regulation of growth and invasiveness of MCF-7 breast cancer cells by antiestrogens.
    Cancer Res. 1988 Dec 1;48(23):6764-8 PMID: 2846159
  28. Sphingosylphosphorylcholine is a remarkably potent mitogen for a variety of cell lines.
    Biochem Biophys Res Commun. 1991 Nov 27;181(1):361-6 PMID: 1958205
  29. A ligand for the erbB-2 oncogene product (gp30) induces differentiation of human breast cancer cells.
    Cell Growth Differ. 1992 Jul;3(7):401-11 PMID: 1358180
  30. Phosphatidic acid modulates DNA synthesis, phospholipase C, and platelet-derived growth factor mRNAs in cultured mesangial cells. Role of protein kinase C.
    J Biol Chem. 1990 Aug 25;265(24):14457-63 PMID: 2167317
  31. Mechanisms of growth control in normal and malignant breast epithelium.
    Recent Prog Horm Res. 1989;45:383-435; discussion 435-40 PMID: 2682845
  32. Kinetics of long-chain (sphingoid) base biosynthesis in intact LM cells: effects of varying the extracellular concentrations of serine and fatty acid precursors of this pathway.
    Biochemistry. 1988 Jan 12;27(1):340-5 PMID: 3126810
  33. Sphingosine inhibits phosphatidate phosphohydrolase in human neutrophils by a protein kinase C-independent mechanism.
    J Biol Chem. 1991 Feb 5;266(4):2013-6 PMID: 1989967
  34. The effect of sphingosine and phorbol ester on the signal transduction enzymes and fibronectin release in cell culture.
    Biochim Biophys Acta. 1992 Jun 29;1135(3):295-300 PMID: 1377951
  35. Activation of phospholipase D by sphingoid bases in NG108-15 neural-derived cells.
    J Biol Chem. 1990 Mar 5;265(7):3868-72 PMID: 2303483
  36. The bimodal growth response of Swiss 3T3 cells to the B subunit of cholera toxin is independent of the density of its receptor, ganglioside GM1.
    Exp Cell Res. 1990 Jul;189(1):13-21 PMID: 2347373
  37. Sphingosine 1-phosphate, a specific endogenous signaling molecule controlling cell motility and tumor cell invasiveness.
    Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9686-90 PMID: 1409683
  38. Phospholipase D in cell signalling and its relationship to phospholipase C.
    Life Sci. 1991;48(9):851-66 PMID: 1997787
  39. Cellular ras activity and phospholipid metabolism.
    Cell. 1988 Jan 15;52(1):63-71 PMID: 3278810
  40. Ganglioside GM1 and sphingolipid breakdown products in cellular proliferation and signal transduction pathways.
    Glycoconj J. 1992 Jun;9(3):110-7 PMID: 1422129
  41. Sphingosine-1-phosphate, a metabolite of sphingosine, increases phosphatidic acid levels by phospholipase D activation.
    J Biol Chem. 1992 Nov 15;267(32):23122-8 PMID: 1429659
  42. Multiple non-specific effects of sphingosine on adenylate cyclase and cyclic AMP accumulation in S49 lymphoma cells preclude its use as a specific inhibitor of protein kinase C.
    Biochem J. 1990 Jun 1;268(2):507-11 PMID: 2163616
  43. Regulation of phosphoinositide hydrolysis in cultured astrocytes by sphingosine and psychosine.
    Biochem Biophys Res Commun. 1992 Jul 31;186(2):790-5 PMID: 1323292
  44. Bifunctional role of glycosphingolipids. Modulators for transmembrane signaling and mediators for cellular interactions.
    J Biol Chem. 1990 Nov 5;265(31):18713-6 PMID: 2229037
  45. Inhibition of the insulin receptor tyrosine kinase by sphingosine.
    Biochemistry. 1991 Aug 6;30(31):7747-54 PMID: 1651108
  46. Intracellular calcium release mediated by sphingosine derivatives generated in cells.
    Science. 1990 Jun 29;248(4963):1653-6 PMID: 2163543
  47. MAP kinases: charting the regulatory pathways.
    Science. 1992 Sep 4;257(5075):1355-6 PMID: 1382311
  48. Sphingosine stimulates cellular proliferation via a protein kinase C-independent pathway.
    J Biol Chem. 1990 Jan 5;265(1):76-81 PMID: 2294122
  49. Increases in phosphatidic acid levels accompany sphingosine-stimulated proliferation of quiescent Swiss 3T3 cells.
    J Biol Chem. 1990 Dec 5;265(34):21309-16 PMID: 2250025
  50. Plasma membrane fractions from rat liver contain a phosphatidate phosphohydrolase distinct from that in the endoplasmic reticulum and cytosol.
    J Biol Chem. 1991 Feb 15;266(5):2988-96 PMID: 1993672
  51. Tumor necrosis factor-alpha activates the sphingomyelin signal transduction pathway in a cell-free system.
    Science. 1992 Mar 27;255(5052):1715-8 PMID: 1313189
  52. Inositol trisphosphate and calcium signalling.
    Nature. 1993 Jan 28;361(6410):315-25 PMID: 8381210
  53. Sphingosine-1-phosphate, a putative second messenger, mobilizes calcium from internal stores via an inositol trisphosphate-independent pathway.
    J Biol Chem. 1994 Feb 4;269(5):3181-8 PMID: 8106352
  54. Programmed cell death induced by ceramide.
    Science. 1993 Mar 19;259(5102):1769-71 PMID: 8456305
  55. Stereospecificity of sphingosine-induced intracellular calcium mobilization and cellular proliferation.
    J Biol Chem. 1994 Jul 8;269(27):17924-30 PMID: 8027049
  56. Synaptic vesicle ceramide kinase. A calcium-stimulated lipid kinase that co-purifies with brain synaptic vesicles.
    J Biol Chem. 1989 Aug 25;264(24):14354-60 PMID: 2547795
  57. Sphingosine activation of protein kinases in Jurkat T cells. In vitro phosphorylation of endogenous protein substrates and specificity of action.
    J Biol Chem. 1992 Jul 25;267(21):15246-51 PMID: 1634554
  58. Sphingosine activates cellular diacylglycerol kinase in intact Jurkat cells, a human T-cell line.
    Biochim Biophys Acta. 1993 Sep 8;1169(3):217-24 PMID: 7548113
  59. Regulation of mammary epithelial cell growth in mice and rats.
    Endocr Rev. 1990 Nov;11(4):494-523 PMID: 2292240
  60. Molecular and cellular analysis of basement membrane invasion by human breast cancer cells in Matrigel-based in vitro assays.
    Breast Cancer Res Treat. 1993;24(3):241-55 PMID: 8435479
  61. Growth factors and cancer.
    Science. 1991 Nov 22;254(5035):1146-53 PMID: 1659742
  62. Peptide growth factors are multifunctional.
    Nature. 1988 Mar 17;332(6161):217-9 PMID: 2831460
  63. Lysophosphatidic acid is a chemoattractant for Dictyostelium discoideum amoebae.
    Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1857-61 PMID: 8383331
  64. Influences of sphingosine on two-stage skin tumorigenesis in Sencar mice.
    Cancer Lett. 1992 Feb 14;62(1):35-42 PMID: 1540929
  65. Subcellular localization and membrane topology of sphingosine-1-phosphate lyase in rat liver.
    J Biol Chem. 1991 Jul 5;266(19):12502-7 PMID: 2061324
  66. Metabolism of sphingosine bases. XV. Enzymatic degradation of 4t-sphingenine 1-phosphate (sphingosine 1-phosphate) to 2t-hexadecen-1-al and ethanolamine phosphate.
    Hoppe Seylers Z Physiol Chem. 1970 Aug;351(8):1041-9 PMID: 4317971
  67. Intracellular signaling by hydrolysis of phospholipids and activation of protein kinase C.
    Science. 1992 Oct 23;258(5082):607-14 PMID: 1411571
  68. Growth factor-like action of phosphatidic acid.
    Nature. 1986 Sep 11-17;323(6084):171-3 PMID: 3748188
  69. Ceramide stimulates epidermal growth factor receptor phosphorylation in A431 human epidermoid carcinoma cells. Evidence that ceramide may mediate sphingosine action.
    J Biol Chem. 1991 Aug 25;266(24):16092-7 PMID: 1874747
  70. Association of increased basement membrane invasiveness with absence of estrogen receptor and expression of vimentin in human breast cancer cell lines.
    J Cell Physiol. 1992 Mar;150(3):534-44 PMID: 1537883
  71. The effector interactions of p21ras.
    Trends Biochem Sci. 1993 Jul;18(7):250-4 PMID: 8212134
  72. Identification of sphingomyelin turnover as an effector mechanism for the action of tumor necrosis factor alpha and gamma-interferon. Specific role in cell differentiation.
    J Biol Chem. 1991 Jan 5;266(1):484-9 PMID: 1845977
Article Info
Journal
Breast cancer research and treatment
Abbr.
Breast Cancer Res Treat
ISSN
0167-6806
DOI
10.1007/BF00666166
Published
1994-00-00
Pages
337-48
Language
English
Region
Netherlands
NLM ID
8111104
Subset
IM
Grants
NCI NIH HHS · 1P50 CA 58185 · United States
NIGMS NIH HHS · 1RO1 GM43880 · United States
External Links
PubMed source DOI: 10.1007/BF00666166 View journal details
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