The emerging role of lysophosphatidic acid in cancer

Nature Reviews Cancer

Volumn 3, Issue 8, 2003, Pages 582-591

  Mills, Gordon B ^a   Moolenaar, Wouter H ^b  

^a UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^b NETHERLANDS CANCER INSTITUTE   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

G PROTEIN COUPLED RECEPTOR; LOW DENSITY LIPOPROTEIN; LYSOPHOSPHATIDIC ACID; MESSENGER RNA; METALLOPROTEINASE; MITOGEN ACTIVATED PROTEIN KINASE; PHOSPHOLIPID; SPHINGOSINE 1 PHOSPHATE; CELL SURFACE RECEPTOR; HETEROTRIMERIC GUANINE NUCLEOTIDE BINDING PROTEIN; LYSOPHOSPHATIDIC ACID RECEPTOR; LYSOPHOSPHOLIPID; TUMOR MARKER;

ANIMAL MODEL; ASCITES FLUID; BREAST CANCER; CANCER; CELL MIGRATION; CELL PROLIFERATION; CELL SURVIVAL; DIGESTIVE SYSTEM CANCER; ENDOMETRIUM CANCER; ENZYME ACTIVATION; HEAD AND NECK CANCER; MELANOMA; METASTASIS; MOUSE; MULTIPLE MYELOMA; NONHUMAN; PRIORITY JOURNAL; PROSTATE CANCER; REVIEW; SIGNAL TRANSDUCTION; THYROID CANCER; UTERINE CERVIX CANCER; WOUND HEALING; CHEMISTRY; HUMAN; METABOLISM; NEOPLASM; PHYSIOLOGY;

HETEROTRIMERIC GTP-BINDING PROTEINS; HUMANS; LYSOPHOSPHOLIPIDS; NEOPLASMS; RECEPTORS, CELL SURFACE; RECEPTORS, G-PROTEIN-COUPLED; RECEPTORS, LYSOPHOSPHATIDIC ACID; SIGNAL TRANSDUCTION; TUMOR MARKERS, BIOLOGICAL;

EID: 0042887042     PISSN: 1474175X     EISSN: None     Source Type: Journal    
DOI: 10.1038/nrc1143     Document Type: Review

References (126)

1. Hanahan, D. & Weinberg, R. A. The hallmarks of cancer. Cell 100, 57-70 (2000).
2. van Corven, E. J., Groenink, A., Jalink, K., Eichholtz, T. & Moolenaar, W. H. Lysophosphatidate-induced cell proliferation: identification and dissection of signaling pathways mediated by G proteins. Cell 59, 45-54 (1989). Seminal observation that LPA has growth-factor-like activities, and signals in a strictly G-protein-dependent manner.
3. Imamura, F. et al. Induction of in vitro tumour cell invasion of cellular monolayers by lysophosphatidic acid or phospholipase D. Biochem. Biophys. Res. Commun. 193, 497-503 (1993).
4. Jalink. K., Hordijk, P. L. & Moolenaar, W. H. Growth factor-like effects of lysophosphatidic acid, a novel lipid mediator. Biochim. Biophys. Acta 1198, 185-196 (1994).
5. Xu, Y., Fang, X. J., Casey, G. & Mills, G. B. Lysophospholipids activate ovarian and breast cancer cells. Biochem. J. 309, 933-940 (1995).
6. Xu, Y., Casey, G. & Mills, G. B. Effect of lysophospholipids on signaling in the human Jurkat T cell line. J. Cell Physiol. 163, 441-450 (1995).
7. Levine, J. S., Koh, J. S., Triaca, V. & Lieberthal, W. Lysophosphatidic acid: a novel growth and survival factor for renal proximal tubular cells. Am. J. Physiol. 273, F575-F585 (1997).
8. Altun-Gultekin, Z. E. et al. Activation of Rho-dependent cell spreading and focal adhesion biogenesis by the v-Crk adaptor protein. Mol. Cell Biol. 18, 3044-3058 (1998).
9. Stam, J. C., Michiels, F., van der Kammen, R. A., Moolenaar, W. H. & Collard, J. G. Invasion of T-lymphoma cells: cooperation between Rho family GTPases and lysophospholipid receptor signaling. EMBO J. 17, 4066-4074 (1998).
10. Weiner, J. A. & Chun, J. Schwann cell survival mediated by the signaling phospholipid lysophosphatidic acid. Proc. Natl Acad. Sci. USA 96, 5233-5238 (1999).
11. Jalink, K., Eichholtz, T., Postma, F. R., van Corven, E. J. & Moolenaar, W. H. Lysophosphatidic acid induces neuronal shape changes via a novel, receptor-mediated signaling pathway: similarity to thrombin action. Cell Growth Differ 4, 247-255 (1993). First demonstration that LPA induces neurite retraction in neuroblastoma cells.
12. Jalink, K., van Corven, E. J., Hengeveld, T, Morii, N., Narumiya, S. & Moolenaar, W. H. Inhibition of lysophosphatidate- and thrombin-induced neurite retraction and neuronal cell rounding by ADP ribosylation of the small GTP-binding protein Rho. J. Cell Biol. 126, 801-810 (1994). First paper indicating a role for RHOA in LPA-induced 'dedifferentiation' of neuroblastoma cells, independently of classic second messengers.
13. Hill, C. S., Oh, S. Y., Schmidt, S. A., Clark, K. J. & Murray. A. W. Lysophosphatidic acid inhibits gap-junctional communication and stimulates phosphorylation of connexin-43 in WB cells: possible involvement of the mitogen-activated protein kinase cascade. Biochem. J. 303, 475-479 (1994).
14. 2- signaling and Rho. J. Neurochem. 66, 537-548 (1996).
15. Schulze, C., Smales, C., Rubin, L. L. & Staddon, J. M. Lysophosphatidic acid increases tight junction permeability in cultured brain endothelial cells. J. Neurochem. 68, 991-1000 (1997).
16. Postma, F. R. et al. Acute loss of cell-cell communication caused by G protein-coupled receptors: a critical role for c-Src. J. Cell Biol. 140, 1199-1209 (1998).
17. van Nieuw Amerongen, G. P., Vermeer, M. A. & van Hinsbergh, V. W. Role of RhoA and Rho kinase in lysophosphatidic acid-induced endothelial barrier dysfunction. Arterioscler. Thromb. Vasc. Biol. 20, E127-E133 (2000).
18. Pustilnik, T. B. et al. Lysophosphatidic acid induces urokinase secretion by ovarian cancer cells. Clin. Cancer Res. 5, 3704-3710 (1999).
19. Palmetshofer, A., Robson, S. C. & Nehls, V. Lysophosphatidic acid activates nuclear factor kappa B and induces proinflammatory gene expression in endothelial cells. Thromb. Haemost. 82, 1532-1537 (1999).
20. Schwartz, B. M. et al. Lysophospholipids increase interleukin-8 expression in ovarian cancer cells, Gynecol. Oncol. 81, 291-300 (2001).
21. Fishman, D. A., Liu, Y., Ellerbroek, S. M. & Stack, M. S. Lysophosphatidic acid promotes matrix metalloproteinase (MMP) activation and MMP-dependent invasion in ovarian cancer cells. Cancer Res. 61, 3194-3199 (2001).
22. Zheng, Y. Kong, Y. & Goetzl, E. J. Lysophosphatidic acid receptor-selective effects on Jurkat T cell migration through a Matrigel model basement membrane. J. Immunol. 166, 2317-2322 (2001).
23. Hu, Y, L. et al. Lysophosphatidic acid induction of vascular endothelial growth factor expression in human ovarian cancer cells. J. Natl Cancer Inst. 93, 762-768 (2001).
24. Gschwind, A., Hart, S., Fischer, O. M. & Ullrich, A. TACE cleavage of proamphiregulin regulates GPCR-induced proliferation and motility of cancer cells. EMBO J. 22, 2411-2421 (2003). Novel mechanism for transactivation of tyrosine-kinase receptors by G-protein-coupled receptors.
25. Fang, X. et al. Mechanisms of lysophosphatidic acid-induced cytokine production in ovarian cancer cells. J. Biol. Chem. (in the press).
26. Sturm, A., Sudermann, T., Schulte, K. M., Goebell, H. & Dignass, A. U. Modulation of intestinal epithelial wound healing in vitro and in vivo by lysophosphatidic acid. Gastroenterology 117, 368-377 (1999).
27. Lee, H., Goetzl, E. J. & An, S. Lysophosphatidic acid and sphingosine 1-phosphate stimulate endothelial cell wound healing. Am. J. Physiol. Cell Physiol. 278, C612-C618 (2000).
28. Watsky, M. A., Griffith, M., Wang, D. A. & Tigyi, G. J. Phospholipid growth factors and corneal wound healing. Ann. NY Acad. Sci. 905, 142-158 (2000).
29. Balazs, L., Okolicany, J., Ferrebee, M., Tolley, B. & Tigy, G. Topical application of the phospholipid growth factor lysophosphatidic acid promotes wound healing in vivo. Am. J. Physiol. Regul. Integr. Comp. Physiol. 280, R466-R472 (2001).
30. Daub, H., Weiss, F. U., Wallasch, C. & Ullrich, A. Role of transactivation of the EGF receptor in signalling by G-protein-coupled receptors. Nature 379, 557-560 (1996). Demonstration of cross-talk between G-protein-coupled receptors and receptor protein tyrosine kinases.
31. Prenzel, N. et al. EGF receptor transactivation by G-protein-coupled receptors requires metalloproteinase cleavage of proHB-EGF. Nature 402, 884-888 (1999).
32. Hordijk, P. L., Verlaan, I., van Corven, E. J. & Moolenaar, W. H. Protein tyrosine phosphorylation induced by lysophosphatidic acid in Rat-1 fibroblasts. Evidence that phosphorylation of map kinase is mediated by the G-p21 ras pathway. J. Biol. Chem. 269, 645-651 (1994).
33. Kumagai, N., Morri, N., Fujisawa, K., Nemoto, Y., & Narumiya, S. ADP-ribosylation of rho p21 inhibits lysophosphatidic acid-induced protein tyrosine phosphorylation and phosphatidylinositol 3-kinase activation. J. Biol. Chem. 268, 24535-24538 (1993).
34. Holtsberg, F. W. et al. Lysophosphatidic acid induces necrosis and apoptosis in hippocampal neurons. J. Neurochem. 70, 66-76 (1998).
35. Holtsberg, E. W. et al. Lysophosphatidic acid and apoptosis of nerve growth factor-differentiated PC12 cells. J. Neurosci. Res. 53, 685-696 (1998).
36. Okusa, M. D. et al. Selective blockade of lysophosphatidic acid LPA3 receptors reduces murine renal ischemia-reperfusion injury. Am. J. Physiol. Renal Physiol. 27 May 2003 [epub ahead of print]. Use of receptor-selective LPA agonists and antagonists in vivo to define the function and role of particular LPA receptors in ischaemia reperfusion.
37. Tokumura, A. et al. Lysophosphatidic acids induce proliferation of cultured vascular smooth muscle cells from rat aorta. Am. J. Physiol. 267, C204-C210 (1994).
38. Tokumura, A., Yotsumoto, T., Masuda, Y. & Tanaka, S. Vasopressor effect of lysophosphatidic acid on spontaneously hypertensive rats and Wistar Kyoto rats. Res. Commun. Mol. Pathol. Pharmacol. 90, 96-102 (1995).
39. Cerutis, D. R. et al. Lysophosphatidic acid and EGF stimulate mitogenesis in human airway smooth muscle cells. Am. J. Physiol. 273, L10-L15 (1997).
40. Toews, M. L., Ustinova, E. E. & Schultz, H. D. Lysophosphatidic acid enhances contractility of isolated airway smooth muscle. J. Appl. Physiol. 83, 1216-1222 (1997).
41. Rizza, C. et al. Lysophosphatidic acid as a regulator of endothelial/leukocyte interaction. Lab. Invest. 79, 1227-1235 (1999).
42. Scalia, R., Pruefer, D. & Lefer, A. M. A novel lysophosphatidic acid analog, LXR-1035, inhibits leukocyte-endothelium interaction via inhibition of cell adhesion molecules. J. Leukoc. Biol. 67, 26-33 (2000).
43. Hayashi, K. et al. Phenotypic modulation of vascular smooth muscle cells induced by unsaturated lysophosphatidic acids. Circ. Res. 89, 251-258 (2001).
44. Natarajan, V., Scribner, W. M., Hart, C. M. & Parthasarathy, S. Oxidized low density lipoprotein-mediated activation of phospholipase D in smooth muscle cells: a possible role in cell proliferation and atherogenesis. J. Lipid Res. 36, 2005-2016 (1995).
45. Siess, W. et al. Lysophosphatidic acid mediates the rapid activation of platelets and endothelial cells by midly oxidized low density lipoprotein and accumulates in human atherosclerotic lesions. Proc. Natl Acad. Sci. USA 96, 6931-6936 (1999). Clear implication of LPA in atherosclerosis.
46. Schmidt, A. et al. Endophilin I mediates synaptic vesicle formation by transfer of arachidonate to lysophosphatidic acid. Nature 401, 133-141 (1999). Demonstration of a potential role for intracellular LPA in vesicle formation.
47. Mclntyre, T. M. et al. Identification of an intracellular receptor for lysophosphatidic acid (LPA): LPA is a transcellular PPARgamma agonist. Proc. Natl Acad. Sci. USA 100, 131-136 (2003). Potential novel function for intracelullar LPA in the activation of the transcription factor PPART.
48. 1 and a putative protein tyrosine kinase.
49. 2- signaling pathways. Curr. Biol. 8, 386-392 (1998). First demonstration that a secreted phospholipase D (of bacterial origin) can generate LPA and activate LPA signalling pathways in mammalian cells.
50. 12/13 subunits in neuronal cells: induction of neurite retraction. Mol. Biol. Cell 10, 1851-1857 (1999).
51. Fang, X. et al. Lysophosphatidic acid prevents apoptosis in fibroblasts via G(i)-protein-mediated activation of mitogen-activated protein kinase. Biochem. J. 352, 135-143 (2000).
52. Fang, X. et al. Lysophospholipid growth factors in the initiation, progression, metastases, and management of ovarian cancer. Ann. NY Acad. Sci. 905, 188-208 (2000).
53. Kranenburg, O. & Moolenaar, W. H. Ras-MAP kinase signalling by lysophosphatidic acid and other G protein-coupled receptor agonists, Oncogene 20, 1540-1546 (2001).
54. Van Leeuwen, F. N. et al. Rac activation by lysophosphatidic acid LPA1 receptors through the guanine nucleotide exchange factor Tiam1 J. Biol. Chem. 278, 400-406 (2003). Shows that LPA1 receptors signal RAC activation and cell migration via the invasion-inducing GDP/GTP exchange factor TIAM1.
55. Etienne-Manneville, S. & Hall, A. Rho GTPases in cell biology. Nature 420, 629-635 (2002).
56. Takeda, H. et al. Pl 3-kinase gamma and protein kinase C-zeta mediate RAS-independent activation of MAP kinase by a Gl protein-coupled receptor. EMBO J. 18, 386-395 (1999).
57. Malliri A. et al. Mice deficient in the Rac activator Tiam1 are resistant to Ras-induced skin tumours. Nature 417, 867-871 (2002).
58. Hecht, J. H., Weiner, J. A., Post, S. R. & Chun, J. 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 (1996). Identification and cloning of the first LPA receptor.
59. An, S., Dickens, M. A., Bleu, T., Hallmark, O. G. & Goetzl, E. J. 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 (1997).
60. An, S., Bleu, T., Hallmark, O. G. & Goetzl, E. J. Characterization of a novel subtype of human G protein-coupled receptor for lysophosphatidic acid. J. Biol. Chem. 273, 7906-7910 (1998). Identification and cloning of the second LPA receptor.
61. Bandoh, K. et al. Molecular cloning and characterization of a novel human G-protein-coupled receptor, EDG7, for lysophosphatidic acid. J. Biol. Chem. 274, 27776-27785 (1999). Cloning of EDG7/LPA3, the third LPA receptor.
62. Im, D. S. et al. Molecular cloning and characterization of a lysophosphatidic acid receptor, Edg-7, expressed in prostate. Mol. Pharmacol. 57, 753-759 (2000). Cloning of the third LPA receptor EDG7/LPA3 from prostate cancer cells.
63. Hla, T., Lee, M. J., Ancellin, N., Paik, J. H. & Kluk, M. J. Lysophospholipids - receptor revelations. Science 294, 1875-1878 (2001).
64. Noguchi, K., Ishii, S. & Shimizu, T. Identification of p2y9/GPR23 as a novel G protein-coupled receptor for lysophosphatidic acid, structurally distant from the Edg family. J. Biol. Chem. 30 Apr 2003 [epub ahead of print]. Identification of the fourth LPA receptor, LPA4.
65. Contos, J. J. & Chun, J. The mouse lp(A3)/Edg7 lysophosphatidic acid receptor gene: genomic structure, chromosomal localization, and expression pattern. Gene 267, 243-253 (2001).
66. Fang, X. et al. Lysophosphatidic acid is a bioactive mediator in ovarian cancer. Biochim. Biophys. Acta 1582, 257-264 (2002).
67. Goetzl, E. J. et al. Distinctive expression and functions of the type 4 endothelial differentiation gene-encoded G protein-coupled receptor for lysophosphatidic acid in ovarian cancer. Cancer Res. 59, 5370-5375 (1999).
68. Furui, T. et al. Overexpression of edg-2/vzg-1 induces apoptosis and anoikis in ovarian cancer cells in a lysophosphatidic acid-independent manner. Clin. Cancer Res. 5, 4308-4318 (1999).
69. Eder, A. M., Sasagawa, T., Mao, M., Aoki, J. & Mills, G. B. Constitutive and lysophosphatidic acid (LPA)-induced LPA production: role of phospholipase D and phospholipase A2. Clin. Cancer Res. 6, 2482-2491 (2000).
70. Schulte, K. M., Beyer, A., Kohrer, K., Oberhauser, S. & Roher, H. D. Lysophosphatidic acid, a novel lipid growth factor for human thyroid cell: over-expression of the high-affinity receptor edg4 in differentiated thyroid cancer. Int. J. Cancer 92, 249-256 (2001).
71. Contos, J. J., Fukushima, N., Weiner, J. A. & Kaushal, D. J. Requirement for the LPA1 lysophosphatidic acid receptor gene in normal suckling behavior. Proc. Natl Acad. Sci. USA 97, 13384-13389 (2000). Shows that Lpa1-knockout mice have reduced viability because of defects in suckling behaviour.
72. Contos, J. J. et al. Characterization of lpa(2) (Edg4) and lpa(1)/lpa(2) (Edg2/Edg4) lysophosphatidic acid receptor knockout mice: signaling deficits without obvious phenotypic abnormality attributable to lpa(2). Mol. Cell Biol. 22, 6921-6929 (2002). Shows that compound Lpa1/Lpa2-knockout mice have a phenotype that is not significantly different from Lpa1-knockout mice. This indicates redundancy in the system and strengthens the likelihood that drugs can be developed against LPA production or function.
73. Shida, D. et al. Lysophosphatidic acid (LPA) enhances the metastatic potential of human colon carcinoma DLD1 cells through LPA1. Cancer Res. 63, 1706-1711 (2003).
74. Fischer, D. J. et al. Naturally occurring analogs of lysophosphatidic acid elicit different cellular responses through selective activation of multiple receptor subtypes. Mol. Pharmacol. 54, 979-988 (1998).
75. Erickson, J. R., Espinal, G. & Mills, G. B. Analysis of the EDG2 receptor based on the structure/activity relationship of LPA. Ann. NY Acad. Sci. 905, 279-281 (2000).
76. Fischer, D. J. et al. Short-chain phosphatidates are subtype-selective antagonists of lysophosphatidic acid receptors. Mol. Pharmacol. 60, 776-784 (2001). Identification of a compound LPA1/LPA3 inhibitor. Low activity and stability limit use to in vitro studies.
77. Wang, D. A. et al. A single amino acid determines lysophospholipid specificity of the S1P1 (EDG1) and LPA1 (EDG2) phospholipid growth factor receptors. J. Biol. Chem. 276, 49213-49220 (2001). Definition of the structural characteristics that determine whether S1P1 and LPA1 will bind their respective ligands.
78. Heise, C. E. et al. Activity of 2-substituted lysophosphatidic acid (LPA) analogs at LPA receptors: discovery of a LPA1/LPA3 receptor antagonist. Mol. Pharmacol. 60, 173-180 (2001). Identification of a composite LPA1/LPA3 receptor antagonist with in vivo activity.
79. Hooks, S. B. et al. Lysophosphatidic acid-induced mitogenesis is regulated by lipid phosphate phosphatases and is Edg-receptor independent. J. Biol. Chem. 276, 4611-4621 (2001).
80. Hasegawa, Y. et al. Identification of a phosphothionate analogue of lysophosphatidic acid (LPA) as a selective agonist of the LPA3 receptor. J. Biol. Chem. 278, 11962-11969 (2003). Identification of a stable agonist of LPA3 with in vivo applicability.
81. Bandoh, K. et al. 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 (2000).
82. Virag, T. et al. Fatty alcohol phosphates are subtype-selective agonists and antagonists of lysophosphatidic acid receptors. Mol. Pharmacol. 63, 1032-1042 (2003). Rational drug design Identifies novel receptor-selective agonists and antagonists.
83. Tigyi, G. & Miledi, R. Lysophosphatidates bound to serum albumin activate membrane currents in Xenopus oocytas and neurite retraction in PC12 pheochromacytoma cells. J. Biol. Chem. 267, 21360-21367 (1992).
84. Goetzl, E. J. at al. Gelsolin binding and cellular presentation of tysophosphatidic acid. J. Biol. Chem. 275, 14573-14578 (2000).
85. Eichholtz, T., Jalink, K., Fahrenfort, I. & Moolenaar, W. H. The bioactive phospholipid lyscphosphatidic acid is released from activated platelets. Biochem. J. 291, 677-680 (1993).
86. Aoki, J. et al. Serum lysophosphatidic acid is produced through diverse phospholipase pathways. J. Biol. Chem. 277, 48737-48744 (2002). Describes the biochemical pathways regulating LPA production in plasma and serum.
87. Sano, T. et al. Multiple mechanisms linked to platelet activation result in lysophosphatidic acid and sphingosine 1-phosphate generation in blood. J. Biol. Chem. 277, 21197-21206 (2002). Elucidation of the mechanisms regulating the production of LPA in plasma and serum.
88. Imai, A., Furui, T., Tamaya, T. & Mills, G. B. Agonadotropin-releasing hormone-responsive phosphatase hydrolyses lysophosphatidic acid within the plasma membrane of ovarian cancer cells. J. Clin. Endocrinol. Metab. 85, 3370-3375 (2000).
89. 2+ control lysophosphatidate signaling through EDG-2 receptors. J. Biol. Chem. 275, 27520-27530 (2000). Strong evidence implicating LPPs in the degradation of LPA and in limiting LPA signalling.
90. Tokumura, A. et al. Identification of human plasma lysophospholipase D, a lysophosphatidic acid-producing enzyme, as autotaxin, a multifunctional phosphodiesterase. J. Biol. Chem. 277, 39436-39442 (2002a).
91. Umezu-Goto, M. et al. Autotaxin has lysophospholipase D activity leading to tumour cell growth and motility by lysophosphatidic acid production. J. Cell Biol. 158, 227-233 (2002). Shows that the long sought after lysoPLD was actually autotaxin. Opened a whole new era in LPA function and potential therapeutic application.
92. Sciorra, V. A. & Morris, A. J. Roles for lipid phosphate phosphatases in regulation of cellular signaling. Biochim. Biophys. Acta 1582, 45-51 (2002).
93. Tanyi, J. L. et al. The human lipid phosphate phosphatase-3 decreases the growth, survival, and tumorigenesis of ovarian cancer cells: validation of the lysophosphatidic acid signaling cascade as a target for therapy in ovarian cancer. Cancer Res. 63, 1073-1082 (2003). Genetic validation of LPA production and action as a therapeutic target in ovarian cancer.
94. Xu, Y. et al. Lysophosphatidic acid as a potential biomarker for ovarian and other gynecologic cancers. JAMA 280, 719-723 (1998). Provocative preliminary data indicating that measurement of lysophospholipids might allow for early diagnosis of cancer.
95. Baker, D. L. et al. Plasma lysophosphatidic acid concentration and ovarian cancer. JAMA 287, 3081-3082 (2002). Careful analysis of the levels of LPA in plasma in ovarian cancer. Failed to confirm that plasma LPA levels are significantly increased in ovarian cancer patients.
96. Hama, K., Bandoh, K., Kakehi, Y., Aoki, J. & Arai, H. Lysophosphatidic acid (LPA) receptors are activated differentially by biological fluids: possible role of LPA-binding proteins in activation of LPA receptors. FEBS Lett. 523, 187-192 (2002).
97. Gerrard, J. M. & Robinson, P. Identification of the molecular species of lysophosphatidic acid produced when platelets are stimulated by thrombin. Biochim. Biophys. Acta 1001, 282-285 (1989).
98. Ginestra, A., Miceli, D., Dolo, V. Romano, F. M. & Vittorelli, M. L. Membrane vesicles in ovarian cancer fluids: a new potential marker. Anticancer Res 19, 3439-3445 (1999).
99. Andre, F. et al. Malignant effusions and immunogenic tumour-derived exosomes. Lancet 360, 295-305 (2002).
100. Stracke, M. L. et al. Identification, purification, and partial sequence analysis of autotaxin, a novel motility-stimulating protein. J. Biol. Chem. 267, 2524-2529 (1992). Identification of autotaxin as a motogen. Autotaxin would eventually be shown to be lysoPLD, the key enzyme regulating LPA production.
101. Murata, J. et al. cDNA cloning of the human tumour motility-stimulating protein, autotaxin, reveals a homology with phosphodiesterases. J. Biol. Chem. 269, 30479-30484 (1994).
102. Nam, S. W. et al. Autotaxin (NPP-2), a metastasis-enhancing motogen, is an angiogenic factor. Cancer Res. 61, 6938-6944 (2001). Describes the role of autotaxin in neovascularization in vivo.
103. Koh, E. et al. Site-directed mutations in the tumor-associated cytokine, autotaxin, eliminate nucleotide phosphodiesterase, lysophospholipase D, and motogenic activities. Cancer Res. 63, 2042-2045 (2003).
104. Clair, T. et al. Autotaxin hydrolyzes phospholipids to produce a migration stimulator, lysophosphatidic acid, or a migration inhibitor, sphingosine-1-phosphate. Cancer Res. (in the press).
105. Gijsbers, R., Aoki, J., Arai, H. & Bollen, M. The hydrolysis of lysophospholipids and nucleotides by autotaxin (NPP2) involves a single catalytic site. FEBS Lett. 538, 60-64 (2003).
106. Bachner, D. et al. Bmp-2 downstream targets in mesenchymal development identified by subtractive cloning from recombinant mesenchymal progenitors (C3H10T1/2). Dev. Dyn. 213, 398-411 (1998).
107. Tice, D. A. et al. Synergistic induction of tumour antigens by Wnt-1 signaling and retinoic acid revealed by gene expression profiling. J. Biol. Chem. 277, 14329-14335 (2002).
108. Croset, M., Brossard, N., Polette, A. & Lagarde, M. Cheracterization of plasma unsaturated lysophosphatidylcholines in human and rat. Biochem. J. 345, 61-67 (2000).
109. Nam, S. W. et al. Autotaxin (ATX), a potent tumour motogen, augments invasive and metastatic potential of ras-transformed cells. Oncogene 19, 241-247 (2000). Describes the role of autotaxin in the metastatic cascade in vivo.
110. Yang, S. Y. et al. Expression of autotaxin (NPP-2) is closely linked to invasiveness of breast cancer cells. Clin. Exp. Metastasis 19, 603-608 (2002).
111. Tanyi, J. L. et al. 2003b Role of decreased levels of LPP-1 in accumulation of lysophosphatidic acid (LPA) in ovarian cancer. Clinical Cancer Res. (in the press).
112. Xie, Y., Gibbs, T. C., Mukhin, Y. V. & Meier, K. E. Role for 18:1 lysophosphatidic acid as an autocnne mediator in prostate cancer cells. J. Biol. Chem. 277, 32516-32526 (2002). Describes an autocrine LPA loop in the stimulation of prostate cancer cells.
113. Mills, G. B., May, C., McGill, M., Roifman, C. & Mellors, A. A putative new growth factor in ascitic fluid from ovarian cancer patients: identification, characterization and mechanism of action. Cancer Res. 48, 1066-1071 (1988).
114. Mills, G. B. et al. Ascitic fluid from human ovarian cancer patients contains growth factors necessary for intraperitoneal growth of human ovanan cancer cells. J. Clin. Invest. 88, 851-855 (1990).
115. Xu, Y. et al. Characterization of an ovarian cancer activating factor (OCAF) in ascites from ovadan cancer patients. Clin. Cancer Res. 1, 1223-1232 (1995). Shows that ascites from ovarian cancer patients contain high levels of bioactive LPA, including unusual LPA isoforms.
116. Westermann, A. M. et al. Malignant effusions contain lysophosphatidic acid (LPA)-like activity. Ann. Oncol. 9, 437-442 (1998).
117. Xiao, Y. J. et al. Electrospray ionization mass spectrometry analysis of lysophospholipids in human ascitic fluids: comparison of the lysophospholipid contents in malignant vs nonmalignant ascitic fluids. Anal. Biochem. 290, 302-813 (2001).
118. Shen, Z., Belinson, J., Morton, R E., Xu, Y. & Xu, Y. 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 (1998).
119. Okita, M. Abnormal plasma lysophosphatidic acid level in ovarian cancer patients. Bulletin of Faculty of Health and Welfare Science, Okayama Prefectural University 1, 29-35 (1994).
120. Sasagawa, T., Suzuki, K., Shiota, T., Kondo, T. & Okita, M. The significance of plasma lysophospholipids in patients with renal failure on hemodialysis. J. Nutr. Sci. Vitaminol. 44, 809-818 (1998).
121. Sasagawa, T., Okita, M., Murakami, J., Kato, T. & Watanabe, A. Abnormal serum lysophospholipids in multiple myeloma patients. Lipids 34, 17-21 (1999).
122. Okita, M., Gaudette, D. C., Mills, G. B. & Holub, B. J. Elevated levels and altered fatty acid composition of plasma lysophosphatidylcholine(lysoPC) in ovarian cancer patients. Int. J. Cancer 71, 31-34 (1997).
123. Yoon, H. R., Kim, H. & Cho, S. H. Quantitative analysis of acyl-lysophosphatidic acid in plasma using negative ionization tandem mass spectrometry. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 788, 85-92 (2003).
124. Shen, Z. et al. Fatty acid composition of lysophosphatidic acid and lysophosphatidylinositol in plasma from patients with ovarian cancer and other gynecological diseases. Gynecol. Oncol. 83, 25-30 (2001).
125. Tokumura, A. et al. Lack of significant differences in the corrected activity of lysophospholipase D, producer of phospholipid mediator lysophosphatidic acid, in incubated serum from women with and without ovarian tumors. Cancer 94, 141-151 (2002).
126. Deng, W. et al. Lysophosphatidic acid protects and rescues intestinal epithelial cells from radiation- and chemotherapy-induced apoptosis. Gastroenterology 123, 206-216 (2002). Indicates that compounds that mimic LPA could decrease toxicity associated with cancer therapy under appropriate conditions.