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Bone and Cancer pp 73–88Cite as

Lysophosphatidic Acid: Role in Bone and Bone Cancer

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Part of the book series: Topics in Bone Biology ((TBB,volume 5))

Abstract

The (1- or 2-)Acyl-lyso-sn-glycero-S-phosphate (LPA) is the simplest glycerophospholipid (Fig. 5.1). LPA derives from the hydrolysis of membrane phospholipids following sequential actions of different phospholipases (PLs) such as PLC, PLA1, PLA2, and lysophospholipase D (LysoPLD/Autotaxin [ATX]) (Fig. 5.1). LPA is formed along two pathways. The first depends on PLC activity. Upon cell activation, the PLC cleaves phosphatidylinositol, releasing inositol triphosphate into the cytoplasm, whereas diacylglycerol (DAG) remains attached to the plasma membrane. DAG then undergoes phosphorylation by the DAG-kinase, to yield phosphatidic acid (PA) which in turn is cleaved by PLA1 or PLA2 into a fatty acid chain (in sn-1 or sn-2 position) and lysophosphatidic acid.

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Abbreviations

μM:

micromolar

ATX:

Autotaxin

Ca2+ :

Calcium

DAG:

Diacylglycerol

Edg:

Endothelial differentiation gene

EGF:

Epithelial growth factor

ER:

Endoplasmic reticulum

ERK:

Extracellular receptor activated kinase

FAK:

Focal adhesion kinase

GPCR:

G protein-coupled receptor

IL-6 IL-8:

Interleukin 6 and 8

LDL:

Low-density lipoprotein

LPA:

Acid lysophosphatidic

LPC:

Lysophosphatidylcholine

LPE:

Lysophosphatidylethanolamine

LPS:

Lysophosphatidylserine

LysoPLD:

Lysophospholipase D

MAPK:

Mitogen-activated protein kinase

M-CSF:

Macrophage colony stimulating factor

nM:

nanomolar

PDGF:

Platelet derived growth factor

PI3K:

Phosphatidyl inositol-3 kinase

PLA2:

Phospholipase A2

PLC:

Phospholipase C

PLD:

Phospholipase D

PTH:

Parathyroid hormone

RANK-L:

Receptor activated nuclear factor-κB ligand

ROCK:

Rho-associated coiled kinase

VEGF:

Vascular endothelial growth factor

References

  1. Agell N, Bachs O, Rocamora N, Villalonga P (2002) Modulation of the Ras/Raf/MEK/ERK pathway by Ca(2+), and calmodulin. Cell Signal 14:649–654.

    Article  PubMed  CAS  Google Scholar 

  2. Ahmed I, Gesty-Palmer D, Drezner MK, Luttrell LM (2003) Transactivation of the epidermal growth factor receptor mediates parathyroid hormone and prostaglandin F2 alpha-stimulated mitogen-activated protein kinase activation in cultured transgenic murine osteoblasts. Mol Endocrinol 17:1607–1621.

    Article  PubMed  CAS  Google Scholar 

  3. An S, Bleu T, Hallmark OG, Goetzl EJ (1998) Characterization of a novel subtype of human G protein-coupled receptor for lysophosphatidic acid. J Biol Chem 273:7906–7910.

    Article  PubMed  CAS  Google Scholar 

  4. An S, Dickens MA, Bleu T, Hallmark OG, Goetzl EJ (1997) Molecular cloning of the human Edg2 protein and its identification as a functional cellular receptor for lysophosphatidic acid. Biochem Biophys Res Commun 231:619–622.

    Article  PubMed  CAS  Google Scholar 

  5. Aoki J, Taira A, Takanezawa Y, Kishi Y, Hama K, Kishimoto T, Mizuno K, Saku K, Taguchi R, Arai H (2002) Serum lysophosphatidic acid is produced through diverse phospholipase pathways. J Biol Chem 277:48737–48744.

    Article  PubMed  CAS  Google Scholar 

  6. Bailon-Plaza A, van der Meulen MC (2003) Beneficial effects of moderate, early loading and adverse effects of delayed or excessive loading on bone healing. J Biomech 36:1069–1077.

    Article  PubMed  Google Scholar 

  7. Bandoh K, Aoki J, Hosono H, Kobayashi S, Kobayashi T, Murakami-Murofushi K, Tsujimoto M, Arai H, Inoue K (1999) Molecular cloning and characterization of a novel human G-protein-coupled receptor, EDG7, for lysophosphatidic acid. J Biol Chem 274:27776–27785.

    Article  PubMed  CAS  Google Scholar 

  8. Bandoh K, Aoki J, Taira A, Tsujimoto M, Arai H, Inoue K (2000) Lysophosphatidic acid (LPA) receptors of the EDG family are differentially activated by LPA species. Structure–activity relationship of cloned LPA receptors. FEBS Lett 478:159–165.

    Article  PubMed  CAS  Google Scholar 

  9. Berridge MJ, Bootman MD, Roderick HL (2003) Calcium signalling: dynamics, homeostasis and remodelling. Nat Rev Mol Cell Biol 4:517–529.

    Article  PubMed  CAS  Google Scholar 

  10. Biswas DK, Shi Q, Baily S, Strickland I, Ghosh S, Pardee AB, Iglehart JD (2004) NF-kappa B activation in human breast cancer specimens and its role in cell proliferation and apoptosis. Proc Natl Acad Sci USA 101:10137–10142.

    Article  PubMed  CAS  Google Scholar 

  11. Boucharaba A, Serre C-M, Gres S, Saulnier-Blache JS, Bordet J-C, Guglielmi J, Clezardin P, Peyruchaud O (2004) Platelet-derived lysophosphatidic acid supports the progression of osteolytic bone metastases in breast cancer. J Clin Invest 114:1714–1725.

    PubMed  CAS  Google Scholar 

  12. Boucharaba A, Serre CM, Guglielmi J, Bordet JC, Clezardin P, Peyruchaud O (2006) The type 1 lysophosphatidic acid receptor is a target for therapy in bone metastases. Proc Natl Acad Sci USA 103:9643–9648.

    Article  PubMed  CAS  Google Scholar 

  13. Brindley DN (2004) Lipid phosphate phosphatases and related proteins: signaling functions in development, cell division, and cancer. J Cell Biochem 92: 900–912.

    Article  PubMed  CAS  Google Scholar 

  14. Carvalho RS, Schaffer JL, Gerstenfeld LC (1998) Osteoblasts induce osteopontin expression in response to attachment on fibronectin: demonstration of a common role for integrin receptors in the signal transduction processes of cell attachment and mechanical stimulation. J Cell Biochem 70:376–390.

    Article  PubMed  CAS  Google Scholar 

  15. Caverzasio J, Palmer G, Suzuki A, Bonjour JP (2000) Evidence for the involvement of two pathways in activation of extracellular signal-regulated kinase (Erk) and cell proliferation by Gi and Gq protein-coupled receptors in osteoblast-like cells. J Bone Miner Res 15:1697–1706.

    Article  PubMed  CAS  Google Scholar 

  16. Chen M, O’Connor KL (2005) Integrin alpha6beta4 promotes expression of autotaxin/ENPP2 autocrine motility factor in breast carcinoma cells. Oncogene 24:5125–5130.

    Article  PubMed  CAS  Google Scholar 

  17. Contos JJA, Fukushima N, Weiner JA, Kaushal D, Chun J (2000) Requirement for the lpA1 lysophosphatidic acid receptor gene in normal suckling behavior. PNAS 97:13384–13389.

    Article  PubMed  CAS  Google Scholar 

  18. Daaka Y (2002) Mitogenic action of LPA in prostate. Biochim Biophys Acta 1582:265–269.

    PubMed  CAS  Google Scholar 

  19. Daub H, Wallasch C, Lankenau A, Herrlich A, Ullrich A (1997) Signal characteristics of G protein-transactivated EGF receptor. EMBO J 16:7032–7044.

    Article  PubMed  CAS  Google Scholar 

  20. Dimitriou R, Tsiridis E, Giannoudis PV (2005) Current concepts of molecular aspects of bone healing. Injury 36:1392–1404.

    Article  PubMed  Google Scholar 

  21. Dziak R, Yang BM, Leung BW, Li S, Marzec N, Margarone J, Bobek L (2003) Effects of sphingosine-1-phosphate and lysophosphatidic acid on human osteoblastic cells. Prostaglandins Leukot Essent Fatty Acids 68:239–249.

    Article  PubMed  CAS  Google Scholar 

  22. Eichholtz T, Jalink K, Fahrenfort I, Moolenaar WH (1993) The bioactive phospholipid lysophosphatidic acid is released from activated platelets. Biochem J 291:677–680.

    PubMed  CAS  Google Scholar 

  23. Einhorn TA (1998) The cell and molecular biology of fracture healing. Clin Orthop Relat Res:S7–21.

    Google Scholar 

  24. Facchini A, Borzi RM, Flamigni F (2005) Induction of ornithine decarboxylase in T/C-28a2 chondrocytes by lysophosphatidic acid: signaling pathway and inhibition of cell proliferation. FEBS Lett 579:2919–2925.

    Article  PubMed  CAS  Google Scholar 

  25. Fang X, Yu S, Bast RC, Liu S, Xu HJ, Hu SX, LaPushin R, Claret FX, Aggarwal BB, Lu Y, Mills GB (2004) Mechanisms for lysophosphatidic acid-induced cytokine production in ovarian cancer cells. J Biol Chem 279:9653–9661.

    Article  PubMed  CAS  Google Scholar 

  26. Ferry G, Tellier E, Try A, Gres S, Naime I, Simon MF, Rodriguez M, Boucher J, Tack I, Gesta S, Chomarat P, Dieu M, Raes M, Galizzi JP, Valet P, Boutin JA, Saulnier-Blache JS (2003) Autotaxin is released from adipocytes, catalyzes lysophosphatidic acid synthesis, and activates preadipocyte proliferation. Up-regulated expression with adipocyte differentiation and obesity. J. Biol. Chem. 278:18162–18169.

    Article  PubMed  CAS  Google Scholar 

  27. Fischer DJ, Nusser N, Virag T, Yokoyama K, Wang D, Baker DL, Bautista D, Parrill AL, Tigyi G (2001) Short-chain phosphatidates are subtype-selective antagonists of lysophosphatidic acid receptors. Mol Pharmacol 60:776–784.

    PubMed  CAS  Google Scholar 

  28. Flamigni F, Stanic I, Facchini A, Cetrullo S, Tantini B, Borzi RM, Guarnieri C, Caldarera CM (2007) Polyamine biosynthesis as a target to inhibit apoptosis of non-tumoral cells. Amino Acids 33:197–202.

    Article  PubMed  CAS  Google Scholar 

  29. Fourcade O, Simon MF, Viode C, Rugani N, Leballe F, Ragab A, Fournie B, Sarda L, Chap H (1995) Secretory phospholipase A2 generates the novel lipid mediator lysophosphatidic acid in membrane microvesicles shed from activated cells. Cell 80:919–927.

    Article  PubMed  CAS  Google Scholar 

  30. Franz-Odendaal TA, Hall BK, Witten PE (2006) Buried alive: how osteoblasts become osteocytes. Dev Dyn 235:176–190.

    Article  PubMed  CAS  Google Scholar 

  31. Freitas F, Jeschke M, Majstorovic I, Mueller DR, Schindler P, Voshol H, Van Oostrum J, Susa M (2002) Fluoroaluminate stimulates phosphorylation of p130 Cas and Fak and increases attachment and spreading of preosteoblastic MC3T3-E1 cells. Bone 30:99–108.

    Article  PubMed  CAS  Google Scholar 

  32. Fukami K, Takenawa T (1992) Phosphatidic acid that accumulates in platelet-derived growth factor-stimulated Balb/c 3T3 cells is a potential mitogenic signal. J. Biol. Chem. 267:10988–10993.

    PubMed  CAS  Google Scholar 

  33. Gennero I, Xuereb JM, Simon MF, Girolami JP, Bascands JL, Chap H, Boneu B, Sie P (1999) Effects of lysophosphatidic acid on proliferation and cytosolic Ca++ of human adult vascular smooth muscle cells in culture. Thromb Res 94:317–326.

    Article  PubMed  CAS  Google Scholar 

  34. Gidley J, Openshaw S, Pring ET, Sale S, Mansell JP (2006) Lysophosphatidic acid cooperates with 1alpha,25(OH)2D3 in stimulating human MG63 osteoblast maturation. Prostaglandins Other Lipid Mediat 80:46–61.

    Article  PubMed  CAS  Google Scholar 

  35. Gobeil F, Jr., Bernier SG, Vazquez-Tello A, Brault S, Beauchamp MH, Quiniou C, Marrache AM, Checchin D, Sennlaub F, Hou X, Nader M, Bkaily G, Ribeiro-da-Silva A, Goetzl EJ, Chemtob S (2003) Modulation of pro-inflammatory gene expression by nuclear lysophosphatidic acid receptor type-1. J Biol Chem 278:38875–38883.

    Article  PubMed  CAS  Google Scholar 

  36. Goetzl EJ, Dolezalova H, Kong Y, Zeng L (1999) Dual mechanisms for lysophospholipid induction of proliferation of human breast carcinoma cells. Cancer Res 59:4732–4737.

    PubMed  CAS  Google Scholar 

  37. Goodship AE, Cunningham JL, Kenwright J (1998) Strain rate and timing of stimulation in mechanical modulation of fracture healing. Clin Orthop Relat Res. 355 Suppl: S105–115.

    Google Scholar 

  38. Grey A, Banovic T, Naot D, Hill B, Callon K, Reid I, Cornish J (2001) Lysophosphatidic acid is an osteoblast mitogen whose proliferative actions involve G(i) proteins and protein kinase C, but not P42/44 mitogen-activated protein kinases. Endocrinology 142: 1098–1106.

    Article  PubMed  CAS  Google Scholar 

  39. Grey A, Chen Q, Callon K, Xu X, Reid IR, Cornish J (2002) The phospholipids sphingosine-1-phosphate and lysophosphatidic acid prevent apoptosis in osteoblastic cells via a signaling pathway involving G(i) proteins and phosphatidylinositol-3 kinase. Endocrinology 143:4755–4763.

    Article  PubMed  CAS  Google Scholar 

  40. Guo C, Luttrell LM, Price DT (2000) Mitogenic signaling in androgen sensitive and insensitive prostate cancer cell lines. J Urol 163:1027–1032.

    Article  PubMed  CAS  Google Scholar 

  41. Guo R, Kasbohm EA, Arora P, Sample CJ, Baban B, Sud N, Sivashanmugam P, Moniri NH, Daaka Y (2006) Expression and function of lysophosphatidic acid LPA1 receptor in prostate cancer cells. Endocrinology 147:4883–4892.

    Google Scholar 

  42. Hahn A, Barth H, Kress M, Mertens PR, Goppelt-Struebe M (2002) Role of Rac and Cdc42 in lysophosphatidic acid-mediated cyclo-oxygenase-2 gene expression. Biochem J 362:33–40.

    Article  PubMed  CAS  Google Scholar 

  43. Hama K, Aoki J, Fukaya M, Kishi Y, Sakai T, Suzuki R, Ohta H, Yamori T, Watanabe M, Chun J, Arai H (2004) Lysophosphatidic acid and autotaxin stimulate cell motility of neoplastic and non-neoplastic cells through LPA1. J Biol Chem 279:17634–17639.

    Article  PubMed  CAS  Google Scholar 

  44. Hecht JH, Weiner JA, Post SR, Chun J (1996) Ventricular zone gene-1 (vzg-1) encodes a lysophosphatidic acid receptor expressed in neurogenic regions of the developing cerebral cortex. J Cell Biol 135: 1071–1083.

    Article  PubMed  CAS  Google Scholar 

  45. Heise CE, Santos WL, Schreihofer AM, Heasley BH, Mukhin YV, Macdonald TL, Lynch KR (2001) Activity of 2-substituted lysophosphatidic acid (LPA) analogs at LPA receptors: discovery of a LPA1/LPA3 receptor antagonist. Mol Pharmacol 60:1173–1180.

    PubMed  CAS  Google Scholar 

  46. Hillner BE, Ingle JN, Berenson JR, Janjan NA, Albain KS, Lipton A, Yee G, Biermann JS, Chlebowski RT, Pfister DG (2000) American Society of Clinical Oncology guideline on the role of bisphosphonates in breast cancer. American Society of Clinical Oncology Bisphosphonates Expert Panel. J Clin Oncol 18: 1378–1391.

    PubMed  CAS  Google Scholar 

  47. Im DS, Heise CE, Ancellin N, O’Dowd BF, Shei GJ, Heavens RP, Rigby MR, Hla T, Mandala S, McAllister G, George SR, Lynch KR (2000) Characterization of a novel sphingosine 1-phosphate receptor, Edg-8. J Biol Chem 275:14281–14286.

    Article  PubMed  CAS  Google Scholar 

  48. Im DS, Heise CE, Harding MA, George SR, O’Dowd BF, Theodorescu D, Lynch KR (2000) Molecular cloning and characterization of a lysophosphatidic acid receptor, Edg-7, expressed in prostate. Mol Pharmacol 57:753–759.

    PubMed  CAS  Google Scholar 

  49. Iqbal J, Zaidi M (2005) Molecular regulation of mechanotransduction. Biochem Biophys Res Commun 328:751–755.

    Article  PubMed  CAS  Google Scholar 

  50. Ishii I, Fukushima N, Ye X, Chun J (2004) Lysophospholipid receptors: signaling and biology. Annu Rev Biochem 73:321–354.

    Article  PubMed  CAS  Google Scholar 

  51. Jalink K, van Corven E, Moolenaar W (1990) Lysophosphatidic acid, but not phosphatidic acid, is a potent Ca2(+)-mobilizing stimulus for fibroblasts. Evidence for an extracellular site of action. J. Biol. Chem. 265:12232–12239.

    PubMed  CAS  Google Scholar 

  52. Jun DJ, Lee JH, Choi BH, Koh TK, Ha DC, Jeong MW, Kim KT (2006) Sphingosine-1-phosphate modulates both lipolysis and leptin production in differentiated rat white adipocytes. Endocrinology 147:5835–5844.

    Article  PubMed  CAS  Google Scholar 

  53. Kaplan AD, Kilkenny DM, Hill DJ, Dixon SJ (1996) Extracellular nucleotides act through P2U purinoceptors to elevate [Ca2+]i and enhance basic fibroblast growth factor-induced proliferation in sheep chondrocytes. Endocrinology 137:4757–4766.

    Article  PubMed  CAS  Google Scholar 

  54. Karagiosis SA, Karin NJ (2007) Lysophosphatidic acid induces osteocyte dendrite outgrowth. Biochem Biophys Res Commun 357:194–199.

    Article  PubMed  CAS  Google Scholar 

  55. Karagiosis SA, Karin NJ (2007) Lysophosphatidic acid induces osteocyte dendrite outgrowth. Biochem Biophys Res Commun 357:194–199

    Google Scholar 

  56. Kehlen A, Englert N, Seifert A, Klonisch T, Dralle H, Langner J, Hoang-Vu C (2004) Expression, regulation and function of autotaxin in thyroid carcinomas. Int J Cancer 109:833–838.

    Article  PubMed  CAS  Google Scholar 

  57. Kim MK, Lee HY, Park KS, Shin EH, Jo SH, Yun J, Lee SW, Yoo YH, Lee YS, Baek SH, Bae YS (2005) Lysophosphatidic acid stimulates cell proliferation in rat chondrocytes. Biochem Pharmacol 70:1764–1771.

    Article  PubMed  CAS  Google Scholar 

  58. Kitayama J, Shida D, Sako A, Ishikawa M, Hama K, Aoki J, Arai H, Nagawa H (2004) Over-expression of lysophosphatidic acid receptor-2 in human invasive ductal carcinoma. Breast Cancer Res 6:R640–646.

    Article  PubMed  CAS  Google Scholar 

  59. Knothe Tate ML, Adamson JR, Tami AE, Bauer TW (2004) The osteocyte. Int J Biochem Cell Biol 36:1–8.

    Article  PubMed  CAS  Google Scholar 

  60. Koh JS, Lieberthal W, Heydrick S, Levine JS (1998) Lysophosphatidic acid is a major serum noncytokine survival factor for murine macrophages which acts via the phosphatidylinositol 3-kinase signaling pathway. J Clin Invest 102:716–727.

    Article  PubMed  CAS  Google Scholar 

  61. Koolpe M, Rodrigo JJ, Benton HP (1998) Adenosine 5ʹ-triphosphate, uridine 5ʹ-triphosphate, bradykinin, and lysophosphatidic acid induce different patterns of calcium responses by human articular chondrocytes. J Orthop Res 16:217–226.

    Article  PubMed  CAS  Google Scholar 

  62. Kotarsky K, Boketoft A, Bristulf J, Nilsson NE, Norberg A, Hansson S, Sillard R, Owman C, Leeb-Lundberg FLM, Olde B (2006) Lysophosphatidic acid binds to and activates GPR92, a G protein-coupled receptor highly expressed in gastro-intestinal lymphocytes. J Pharmacol Exp Ther:jpet.105.098848.

    Google Scholar 

  63. Kue PF, Taub JS, Harrington LB, Polakiewicz RD, Ullrich A, Daaka Y (2002) Lysophosphatidic acid-regulated mitogenic ERK signaling in androgen-insensitive prostate cancer PC-3 cells. Int J Cancer 102:572–579.

    Article  PubMed  CAS  Google Scholar 

  64. Kuhn K, D’Lima DD, Hashimoto S, Lotz M (2004) Cell death in cartilage. Osteoarthritis Cartilage 12:1–16.

    Article  PubMed  CAS  Google Scholar 

  65. Leach JK, Kaigler D, Wang Z, Krebsbach PH, Mooney DJ (2006) Coating of VEGF-releasing scaffolds with bioactive glass for angiogenesis and bone regeneration. Biomaterials 27:3249–3255.

    Article  PubMed  CAS  Google Scholar 

  66. Lee CW, Nam JS, Park YK, Choi HK, Lee JH, Kim NH, Cho J, Song DK, Suh HW, Lee J, Kim YH, Huh SO (2003) Lysophosphatidic acid stimulates CREB through mitogen- and stress-activated protein kinase-1. Biochem Biophys Res Commun 305: 455–461.

    Article  PubMed  CAS  Google Scholar 

  67. Lee H, Goetzl EJ, An S (2000) Lysophosphatidic acid and sphingosine 1-phosphate stimulate endothelial cell wound healing. Am J Physiol Cell Physiol 278: C612–618.

    PubMed  CAS  Google Scholar 

  68. Lee HY, Murata J, Clair T, Polymeropoulos MH, Torres R, Manrow RE, Liotta LA, Stracke ML (1996) Cloning, chromosomal localization, and tissue expression of autotaxin from human teratocarcinoma cells. Biochem Biophys Res Commun 218:714–719.

    Article  PubMed  CAS  Google Scholar 

  69. Lee MJ, Van Brocklyn JR, Thangada S, Liu CH, Hand AR, Menzeleev R, Spiegel S, Hla T (1998) Sphingosine-1-phosphate as a ligand for the G protein-coupled receptor EDG-1. Science 279:1552–1555.

    Article  PubMed  CAS  Google Scholar 

  70. Leung BP, Xu D, Culshaw S, McInnes IB, Liew FY (2004) A novel therapy of murine collagen-induced arthritis with soluble T1/ST2. J Immunol 173:145–150.

    PubMed  CAS  Google Scholar 

  71. Li Y, Sarkar FH (2002) Down-regulation of invasion and angiogenesis-related genes identified by cDNA microarray analysis of PC3 prostate cancer cells treated with genistein. Cancer Lett 186:157–164.

    Article  PubMed  CAS  Google Scholar 

  72. Liliom K, Guan Z, Tseng JL, Desiderio DM, Tigyi G, Watsky MA (1998) Growth factor-like phospholipids generated after corneal injury. Am J Physiol 274:C1065–1074.

    PubMed  CAS  Google Scholar 

  73. Liu R, Farach-Carson MC, Karin NJ (1995) Effects of sphingosine derivatives on MC3T3-E1 pre-osteoblasts: psychosine elicits release of calcium from intracellualr stores. Biochem Biophys Res Commun 214:676–684.

    Article  PubMed  CAS  Google Scholar 

  74. Lynch MA, Petrel TA, Song H, Knobloch TJ, Casto BC, Ramljak D, Anderson LM, DeGroff V, Stoner GD, Brueggemeier RW, Weghorst CM (2001) Responsiveness to transforming growth factor-beta (TGF-beta)-mediated growth inhibition is a function of membrane-bound TGF-beta type II receptor in human breast cancer cells. Gene Expr 9:157–171.

    PubMed  CAS  Google Scholar 

  75. Lyons JM, Karin NJ (2001) A role for G protein-coupled lysophospholipid receptors in sphingolipid-induced Ca2+ signaling in MC3T3-E1 osteoblastic cells. J Bone Miner Res 16:2035–2042.

    Article  PubMed  CAS  Google Scholar 

  76. MacLennan AJ, Carney PR, Zhu WJ, Chaves AH, Garcia J, Grimes JR, Anderson KJ, Roper SN, Lee N (2001) An essential role for the H218/AGR16/Edg-5/LP(B2) sphingosine 1-phosphate receptor in neuronal excitability. Eur J Neurosci 14:203–209.

    Article  PubMed  CAS  Google Scholar 

  77. Manolagas SC (2000) Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. Endocr Rev 21:115–137.

    Article  PubMed  CAS  Google Scholar 

  78. Marriott I (2004) Osteoblast responses to bacterial pathogens: a previously unappreciated role for bone-forming cells in host defense and disease progression. Immunol Res 30:291–308.

    Article  PubMed  CAS  Google Scholar 

  79. Masiello LM, Fotos JS, Galileo DS, Karin NJ (2006) Lysophosphatidic acid induces chemotaxis in MC3T3-E1 osteoblastic cells. Bone 39:72–82.

    Article  PubMed  CAS  Google Scholar 

  80. McIntyre TM, Pontsler AV, Silva AR, St. Hilaire A, Xu Y, Hinshaw JC, Zimmerman GA, Hama K, Aoki J, Arai H, Prestwich GD (2003) From the Cover: Identification of an intracellular receptor for lysophosphatidic acid (LPA): LPA is a transcellular PPARgamma agonist. PNAS 100:131–136.

    Article  PubMed  CAS  Google Scholar 

  81. Meloche S, Pouyssegur J (2007) The ERK1/2 mitogen-activated protein kinase pathway as a master regulator of the G1- to S-phase transition. Oncogene 26: 3227–3239.

    Article  PubMed  CAS  Google Scholar 

  82. Mills GB, Moolenaar WH (2003) The emerging role of lysophosphatidic acid in cancer. Nat Rev Cancer 3: 582–591.

    Article  PubMed  CAS  Google Scholar 

  83. Moolenaar WH (2000) Development of our current understanding of bioactive lysophospholipids. Ann N Y Acad Sci 905:1–10.

    Article  PubMed  CAS  Google Scholar 

  84. Moolenaar WH, van Meeteren LA, Giepmans BN (2004) The ins and outs of lysophosphatidic acid signaling. Bioessays 26:870–881.

    Article  PubMed  CAS  Google Scholar 

  85. Mundy GR (2002) Metastasis to bone: causes, consequences and therapeutic opportunities. Nat Rev Cancer 2:584–593.

    Article  PubMed  CAS  Google Scholar 

  86. Nevalainen TJ (1993) Serum phospholipases A2 in inflammatory diseases. Clin Chem 39:2453–2459.

    PubMed  CAS  Google Scholar 

  87. Noguchi K, Ishii S, Shimizu T (2003) Identification of p2y9/GPR23 as a novel G protein-coupled receptor for lysophosphatidic acid, structurally distant from the Edg family. J. Biol. Chem. 278:25600–25606.

    Article  PubMed  CAS  Google Scholar 

  88. Ohata H, Ikeuchi T, Kamada A, Yamamoto M, Momose K (2001) Lysophosphatidic acid positively regulates the fluid flow-induced local Ca(2+) influx in bovine aortic endothelial cells. Circ Res 88:925–932.

    Article  PubMed  CAS  Google Scholar 

  89. Ohta H, Sato K, Murata N, Damirin A, Malchinkhuu E, Kon J, Kimura T, Tobo M, Yamazaki Y, Watanabe T, Yagi M, Sato M, Suzuki R, Murooka H, Sakai T, Nishitoba T, Im DS, Nochi H, Tamoto K, Tomura H, Okajima F (2003) Ki16425, a subtype-selective antagonist for EDG-family lysophosphatidic acid receptors. Mol Pharmacol 64:994–1005.

    Article  PubMed  CAS  Google Scholar 

  90. Ohtsu H, Dempsey PJ, Eguchi S (2006) ADAMs as mediators of EGF receptor transactivation by G protein-coupled receptors. Am J Physiol Cell Physiol 291:C1–10.

    Article  PubMed  CAS  Google Scholar 

  91. Pages C, Daviaud D, An S, Krief S, Lafontan M, Valet P, Saulnier-Blache JS (2001) Endothelial differentiation gene-2 receptor is involved in lysophosphatidic acid-dependent control of 3T3F442A preadipocyte proliferation and spreading. J Biol Chem 276:11599–11605.

    Article  PubMed  CAS  Google Scholar 

  92. Palmetshofer A, Robson SC, Nehls V (1999) Lysophosphatidic acid activates nuclear factor kappa B and induces proinflammatory gene expression in endothelial cells. Thromb Haemost 82:1532–1537.

    PubMed  CAS  Google Scholar 

  93. Panupinthu N, Zhao L, Possmayer F, Ke HZ, Sims SM, Dixon SJ (2007) P2X7 Nucleotide receptors mediate blebbing in osteoblasts through a pathway involving lysophosphatidic acid. J. Biol. Chem. 282:3403–3412.

    Article  PubMed  CAS  Google Scholar 

  94. Pecheur I, Peyruchaud O, Serre CM, Guglielmi J, Voland C, Bourre F, Margue C, Cohen-Solal M, Buffet A, Kieffer N, Clezardin P (2002) Integrin alpha(v)beta3 expression confers on tumor cells a greater propensity to metastasize to bone. Faseb J 16:1266–1268.

    PubMed  CAS  Google Scholar 

  95. Pegg AE (2006) Regulation of ornithine decarboxylase. J Biol Chem 281:14529–14532.

    Article  PubMed  CAS  Google Scholar 

  96. Pruzanski W, Keystone EC, Sternby B, Bombardier C, Snow KM, Vadas P (1988) Serum phospholipase A2 correlates with disease activity in rheumatoid arthritis. J Rheumatol 15:1351–1355.

    PubMed  CAS  Google Scholar 

  97. Radeff-Huang J, Seasholtz TM, Matteo RG, Brown JH (2004) G protein mediated signaling pathways in lysophospholipid induced cell proliferation and survival. J Cell Biochem 92:949–966.

    Article  PubMed  CAS  Google Scholar 

  98. Raj GV, Sekula JA, Guo R, Madden JF, Daaka Y (2004) Lysophosphatidic acid promotes survival of androgen-insensitive prostate cancer PC3 cells via activation of NF-kappaB. Prostate 61:105–113.

    Article  PubMed  CAS  Google Scholar 

  99. Rubin J, Rubin C, Jacobs CR (2006) Molecular pathways mediating mechanical signaling in bone. Gene 367:1–16.

    Article  PubMed  CAS  Google Scholar 

  100. Sano T, Baker D, Virag T, Wada A, Yatomi Y, Kobayashi T, Igarashi Y, Tigyi G (2002) Multiple mechanisms linked to platelet activation result in lysophosphatidic acid and sphingosine 1-phosphate generation in blood. J Biol Chem 277:21197–21206.

    Article  PubMed  CAS  Google Scholar 

  101. Sardar VM, Bautista DL, Fischer DJ, Yokoyama K, Nusser N, Virag T, Wang DA, Baker DL, Tigyi G, Parrill AL (2002) Molecular basis for lysophosphatidic acid receptor antagonist selectivity. Biochim Biophys Acta 1582:309–317.

    PubMed  CAS  Google Scholar 

  102. Sayas CL, Avila J, Wandosell F (2002) Regulation of neuronal cytoskeleton by lysophosphatidic acid: role of GSK-3. Biochim Biophys Acta 1582:144–153.

    PubMed  CAS  Google Scholar 

  103. Schulte KM, Beyer A, Kohrer K, Oberhauser S, Roher HD (2001) Lysophosphatidic acid, a novel lipid growth factor for human thyroid cells: over-expression of the high-affinity receptor edg4 in differentiated thyroid cancer. Int J Cancer 92:249–256.

    Article  PubMed  CAS  Google Scholar 

  104. Shen Z, Belinson J, Morton RE, Xu Y (1998) Phorbol 12-myristate 13-acetate stimulates lysophosphatidic acid secretion from ovarian and cervical cancer cells but not from breast or leukemia cells. Gynecol Oncol 71:364–368.

    Article  PubMed  CAS  Google Scholar 

  105. Shida D, Kitayama J, Yamaguchi H, Okaji Y, Tsuno NH, Watanabe T, Takuwa Y, Nagawa H (2003) Lysophosphatidic acid (LPA) enhances the metastatic potential of human colon carcinoma DLD1 cells through LPA1. Cancer Res 63:1706–1711.

    PubMed  CAS  Google Scholar 

  106. Shida D, Watanabe T, Aoki J, Hama K, Kitayama J, Sonoda H, Kishi Y, Yamaguchi H, Sasaki S, Sako A, Konishi T, Arai H, Nagawa H (2004) Aberrant expression of lysophosphatidic acid (LPA) receptors in human colorectal cancer. Lab Invest 84:1352–1362.

    Article  PubMed  CAS  Google Scholar 

  107. Siess W, Tigyi G (2004) Thrombogenic and atherogenic activities of lysophosphatidic acid. J Cell Biochem 92:1086–1094.

    Article  PubMed  CAS  Google Scholar 

  108. Siess W, Zangl KJ, Essler M, Bauer M, Brandl R, Corrinth C, Bittman R, Tigyi G, Aepfelbacher M (1999) Lysophosphatidic acid mediates the rapid activation of platelets and endothelial cells by mildly oxidized low density lipoprotein and accumulates in human atherosclerotic lesions. Proc Natl Acad Sci USA 96:6931–6936.

    Article  PubMed  CAS  Google Scholar 

  109. Stracke ML, Krutzsch HC, Unsworth EJ, Arestad A, Cioce V, Schiffmann E, Liotta LA (1992) Identification, purification, and partial sequence analysis of autotaxin, a novel motility-stimulating protein. J Biol Chem 267:2524–2529.

    PubMed  CAS  Google Scholar 

  110. Street J, Bao M, deGuzman L, Bunting S, Peale FV, Jr., Ferrara N, Steinmetz H, Hoeffel J, Cleland JL, Daugherty A, van Bruggen N, Redmond HP, Carano RA, Filvaroff EH (2002) Vascular endothelial growth factor stimulates bone repair by promoting angiogenesis and bone turnover. Proc Natl Acad Sci USA 99: 9656–9661.

    Article  PubMed  CAS  Google Scholar 

  111. Tabata K, Baba K, Shiraishi A, Ito M, Fujita N (2007) The orphan GPCR GPR87 was deorphanized and shown to be a lysophosphatidic acid receptor. Biochem Biophys Res Commun 363:861–866.

    Article  PubMed  CAS  Google Scholar 

  112. Tabuchi S, Kume K, Aihara M, Shimizu T (2000) Expression of lysophosphatidic acid receptor in rat astrocytes: mitogenic effect and expression of neurotrophic genes. Neurochem Res 25:573–582.

    Article  PubMed  CAS  Google Scholar 

  113. Tanaka M, Okudaira S, Kishi Y, Ohkawa R, Iseki S, Ota M, Noji S, Yatomi Y, Aoki J, Arai H (2006) Autotaxin stabilizes blood vessels and is required for embryonic vasculature by producing lysophosphatidic acid. J Biol Chem 281:25822–25830.

    Google Scholar 

  114. Themistocleous GS, Kontou SE, Lembessis P, Katopodis HA, Kaseta MA, Themistocleous MS, Koutsilieris M (2003) Skeletal growth factor involvement in the regulation of fracture healing process. In Vivo 17:489–503.

    PubMed  CAS  Google Scholar 

  115. Tokumura A (2004) Metabolic pathways and physiological and pathological significances of lysolipid phosphate mediators. J Cell Biochem 92:869–881.

    Article  PubMed  CAS  Google Scholar 

  116. Trajkovic V, Sweet MJ, Xu D (2004) T1/ST2 – an IL-1 receptor-like modulator of immune responses. Cytokine Growth Factor Rev 15:87–95.

    Article  PubMed  CAS  Google Scholar 

  117. Umezu-Goto M, Kishi Y, Taira A, Hama K, Dohmae N, Takio K, Yamori T, Mills GB, Inoue K, Aoki J, Arai H (2002) Autotaxin has lysophospholipase D activity leading to tumor cell growth and motility by lysophosphatidic acid production. J Cell Biol 158:227–233.

    Article  PubMed  CAS  Google Scholar 

  118. Valet P, Pages C, Jeanneton O, Daviaud D, Barbe P, Record M, Saulnier-Blache JS, Lafontan M (1998) Alpha2-adrenergic receptor-mediated release of lysophosphatidic acid by adipocytes. A paracrine signal for preadipocyte growth. J Clin Invest 101:1431–1438.

    Article  PubMed  CAS  Google Scholar 

  119. Van Brocklyn JR, Graler MH, Bernhardt G, Hobson JP, Lipp M, Spiegel S (2000) Sphingosine-1-phosphate is a ligand for the G protein-coupled receptor EDG-6. Blood 95:2624–2629.

    PubMed  Google Scholar 

  120. van Dijk MC, Postma F, Hilkmann H, Jalink K, van Blitterswijk WJ, Moolenaar WH (1998) Exogenous phospholipase D generates lysophosphatidic acid and activates Ras, Rho and Ca2+ signaling pathways. Curr Biol 8:386–392.

    Article  PubMed  Google Scholar 

  121. van Meeteren LA, Ruurs P, Stortelers C, Bouwman P, van Rooijen MA, Pradere JP, Pettit TR, Wakelam MJO, Saulnier-Blache JS, Mummery CL, Moolenaar WH, Jonkers J (2006) Autotaxin, a secreted lysophospholipase D, is essential for blood vessel formation during development. Mol Cell Biol 26:5015–5022.

    Article  PubMed  CAS  Google Scholar 

  122. Verheijen MH, Defize LH (1995) Parathyroid hormone inhibits mitogen-activated protein kinase activation in osteosarcoma cells via a protein kinase A-dependent pathway. Endocrinology 136:3331–3337.

    Article  PubMed  CAS  Google Scholar 

  123. Verheijen MH, Defize LH (1995) Parathyroid hormone inhibits mitogen-activated protein kinase activation in osteosarcoma cells via a protein kinase A-dependent pathway. Endocrinology 136:3331–3337.

    Article  PubMed  CAS  Google Scholar 

  124. Vogt W (1963) Pharamacologically active acidic phospholipids and glycolipids. Biochem Pharmacol 12:415–420.

    Article  PubMed  CAS  Google Scholar 

  125. Wang L, Cummings R, Zhao Y, Kazlauskas A, Sham JKS, Morris A, Georas S, Brindley DN, Natarajan V (2003) Involvement of phospholipase D2 in lysophosphatidate-induced transactivation of platelet-derived growth factor receptor-{beta} in human bronchial epithelial cells. J Biol Chem 278:39931–39940.

    Article  PubMed  CAS  Google Scholar 

  126. Waters KM, Tan R, Genetos DC, Verma S, Yellowley CE, Karin NJ (2007) DNA microarray analysis reveals a role for lysophosphatidic acid in the regulation of anti-inflammatory genes in MC3T3-E1 cells. Bone 41: 833–841.

    Article  PubMed  CAS  Google Scholar 

  127. Watson SP, McConnell RT, Lapetina EG (1985) Decanoyl lysophosphatidic acid induces platelet aggregation through an extracellular action. Evidence against a second messenger role for lysophosphatidic acid. Biochem J 232:61–66.

    PubMed  CAS  Google Scholar 

  128. Weinberg EO, Shimpo M, De Keulenaer GW, MacGillivray C, Tominaga S, Solomon SD, Rouleau JL, Lee RT (2002) Expression and regulation of ST2, an interleukin-1 receptor family member, in cardiomyocytes and myocardial infarction. Circulation 106:2961–2966.

    Article  PubMed  CAS  Google Scholar 

  129. Xie Y, Gibbs TC, Mukhin YV, Meier KE (2002) Role for 18:1 lysophosphatidic acid as an autocrine mediator in prostate cancer cells. J Biol Chem 277: 32516–32526.

    Article  PubMed  CAS  Google Scholar 

  130. Xing L, Boyce BF (2005) Regulation of apoptosis in osteoclasts and osteoblastic cells. Biochem Biophys Res Commun 328:709–720.

    Article  PubMed  CAS  Google Scholar 

  131. Xu D, Chan WL, Leung BP, Hunter D, Schulz K, Carter RW, McInnes IB, Robinson JH, Liew FY (1998) Selective expression and functions of interleukin 18 receptor on T helper (Th) type 1 but not Th2 cells. J Exp Med 188:1485–1492.

    Article  PubMed  CAS  Google Scholar 

  132. Yang M, Zhong WW, Srivastava N, Slavin A, Yang J, Hoey T, An S (2005) G protein-coupled lysophosphatidic acid receptors stimulate proliferation of colon cancer cells through the {beta}-catenin pathway. PNAS 102:6027–6032.

    Article  PubMed  CAS  Google Scholar 

  133. Yang SY, Lee J, Park CG, Kim S, Hong S, Chung HC, Min SK, Han JW, Lee HW, Lee HY (2002) Expression of autotaxin (NPP-2) is closely linked to invasiveness of breast cancer cells. Clin Exp Metastasis 19: 603–608.

    Article  PubMed  CAS  Google Scholar 

  134. Yukioka K, Wakitani S, Yukioka M, Furumitsu Y, Shichikawa K, Ochi T, Goto H, Matsui-Yuasa I, Otani S, Nishizawa Y, et al. (1992) Polyamine levels in synovial tissues and synovial fluids of patients with rheumatoid arthritis. J Rheumatol 19:689–692.

    PubMed  CAS  Google Scholar 

  135. Zayzafoon M (2006) Calcium/calmodulin signaling controls osteoblast growth and differentiation. J Cell Biochem 97:56–70.

    Article  PubMed  CAS  Google Scholar 

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  1. INSERM Unit 664, Faculté de Médecine Laennec, Lyon, France

    Olivier Peyruchaud

  2. Department of Cell Biology and Biochemistry, Pacific Northwest National Laboratory, Richland, WA, USA

    Norman J. Karin

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Peyruchaud, O., Karin, N.J. (2010). Lysophosphatidic Acid: Role in Bone and Bone Cancer. In: Bone and Cancer. Topics in Bone Biology, vol 5. Springer, London. https://doi.org/10.1007/978-1-84882-019-7_5

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