Cancer and Metastasis Reviews

, 26:359 | Cite as

Inflammation and melanoma growth and metastasis: The role of platelet-activating factor (PAF) and its receptor

  • Vladislava Melnikova
  • Menashe Bar-EliEmail author


An inflammatory tumor microenvironment fosters tumor growth, angiogenesis and metastatic progression. Platelet-activating factor (PAF) is an inflammatory biolipid produced from membrane glycerophospholipids. Through the activity of its G-protein coupled receptor, PAF triggers a variety of pathological reactions including tumor neo-angiogenesis. Several groups have demonstrated that inhibiting PAF-PAF receptor pathway at the level of a ligand or receptor results in an effective inhibition of experimental tumor growth and metastasis. In particular, our group has recently demonstrated that PAF receptor antagonists can effectively inhibit the metastatic potential of human melanoma cells in nude mice. Furthermore, we showed that PAF stimulated the phosphorylation of CREB and ATF-1 in metastatic melanoma cells, which resulted in overexpression of MMP-2 and MT1-MMP. Our data indicate that PAF acts as a promoter of melanoma metastasis in vivo. Since only metastatic melanoma cells overexpress CREB/ATF-1, we propose that these cells are better equipped to respond to PAF within the tumor microenvironment when compared to their non-metastatic counterparts.


Platelet-activating factor CREB Melanoma Metastasis MMP-2 MT1-MMP 


  1. 1.
    Balkwill, F., & Mantovani, A. (2001). Inflammation and cancer: back to Virchow? Lancet, 357(9255), 539–45.PubMedCrossRefGoogle Scholar
  2. 2.
    Coussens, L. M., & Werb, Z. (2002). Inflammation and cancer. Nature, 420(6917), 860–67.PubMedCrossRefGoogle Scholar
  3. 3.
    Mantovani, A. (2005). Cancer: Inflammation by remote control. Nature, 435(7043), 752–53.PubMedCrossRefGoogle Scholar
  4. 4.
    Pikarsky, E., Porat, R. M., Stein, I., Abramovitch, R., Amit, S., Kasem, S., et al. (2004). NF-kappaB functions as a tumour promoter in inflammation-associated cancer. Nature, 431(7007), 461–66.PubMedCrossRefGoogle Scholar
  5. 5.
    Chen, Y. Q., Liu, B., Tang, D. G., & Honn, K. V. (1992). Fatty acid modulation of tumor cell-platelet-vessel wall interaction. Cancer and Metastasis Reviews, 11(3–), 389–09.PubMedCrossRefGoogle Scholar
  6. 6.
    Karpatkin, S., & Pearlstein, E. (1981). Role of platelets in tumor cell metastases. Annals of Internal Medicine, 95(5), 636–41.PubMedGoogle Scholar
  7. 7.
    Honn, K. V., Tang, D. G., & Crissman, J. D. (1992). Platelets and cancer metastasis: A causal relationship? Cancer and Metastasis Reviews, 11(3–), 325–51.PubMedCrossRefGoogle Scholar
  8. 8.
    Nieswandt, B., Hafner, M., Echtenacher, B., & Mannel, D. N. (1999). Lysis of tumor cells by natural killer cells in mice is impeded by platelets. Cancer Research, 59(6), 1295–300.PubMedGoogle Scholar
  9. 9.
    Pinedo, H. M., Verheul, H. M., D’Amato, R. J., & Folkman, J. (1998). Involvement of platelets in tumour angiogenesis? Lancet, 352(9142), 1775–777.PubMedCrossRefGoogle Scholar
  10. 10.
    Robinson, S. C., & Coussens, L. M. (2005). Soluble mediators of inflammation during tumor development. Advances in Cancer Research, 93, 159–87.PubMedCrossRefGoogle Scholar
  11. 11.
    Dauer, D. J., Ferraro, B., Song, L., Yu, B., Mora, L., Buettner, R., et al. (2005). Stat3 regulates genes common to both wound healing and cancer. Oncogene, 24(21), 3397–408.PubMedCrossRefGoogle Scholar
  12. 12.
    Brown, J. R., & DuBois, R. N. (2004). Cyclooxygenase as a target in lung cancer. Clinical Cancer Research, 10(12 Pt 2), 4266s–269s.PubMedCrossRefGoogle Scholar
  13. 13.
    Leslie, M. C., & Bar-Eli, M. (2005). Regulation of gene expression in melanoma: New approaches for treatment. Journal of Cell Biochemistry, 94(1), 25–8.CrossRefGoogle Scholar
  14. 14.
    Amiri, K. I., & Richmond, A. (2005). Role of nuclear factor-kappa B in melanoma. Cancer and Metastasis Reviews, 24(2), 301–13.PubMedCrossRefGoogle Scholar
  15. 15.
    Richmond, A., Balentien, E., Thomas, H. G., Flaggs, G., Barton, D. E., Spiess, J., et al. (1988). Molecular characterization and chromosomal mapping of melanoma growth stimulatory activity, a growth factor structurally related to beta-thromboglobulin. EMBO Journal, 7(7), 2025–033.PubMedGoogle Scholar
  16. 16.
    Claffey, K. P., Brown, L. F., del Aguila, L. F., Tognazzi, K., Yeo, K. T., Manseau, E. J., et al. (1996). Expression of vascular permeability factor/vascular endothelial growth factor by melanoma cells increases tumor growth, angiogenesis, and experimental metastasis. Cancer Research, 56(1), 172–81.PubMedGoogle Scholar
  17. 17.
    Tellez, C., McCarty, M., Ruiz, M., & Bar-Eli, M. (2003). Loss of activator protein-2alpha results in overexpression of protease-activated receptor-1 and correlates with the malignant phenotype of human melanoma. Journal of Biological Chemistry, 278(47), 46632–6642.PubMedCrossRefGoogle Scholar
  18. 18.
    Tellez, C. S., Davis, D. W., Prieto, V. G., Gershenwald, J. E., Johnson, M. M., McCarty, M. F., et al. (2007). Quantitative analysis of melanocytic tissue array reveals inverse correlation between activator protein-2alpha and protease-activated receptor-1 expression during melanoma progression. Journal of Investigative Dermatology, 127(2), 387–93.PubMedCrossRefGoogle Scholar
  19. 19.
    Tellez, C., & Bar-Eli, M. (2003). Role and regulation of the thrombin receptor (PAR-1) in human melanoma. Oncogene, 22(20), 3130–137.PubMedCrossRefGoogle Scholar
  20. 20.
    Lorant, D. E., Patel, K. D., McIntyre, T. M., McEver, R. P., Prescott, S. M., & Zimmerman, G. A. (1991). Coexpression of GMP-140 and PAF by endothelium stimulated by histamine or thrombin: A juxtacrine system for adhesion and activation of neutrophils. Journal of Cell Biology, 115(1), 223–34.PubMedCrossRefGoogle Scholar
  21. 21.
    Zimmerman, G. A., McIntyre, T. M., Mehra, M., & Prescott, S. M. (1990). Endothelial cell-associated platelet-activating factor: A novel mechanism for signaling intercellular adhesion. Journal of Cell Biology, 110(2), 529–40.PubMedCrossRefGoogle Scholar
  22. 22.
    Zimmerman, G. A., McIntyre, T. M., Prescott, S. M., & Stafforini, D. M. (2002) The platelet-activating factor signaling system and its regulators in syndromes of inflammation and thrombosis. Critical Care Medicine, 30(5 Suppl), S294’S301.PubMedCrossRefGoogle Scholar
  23. 23.
    Bennett, S. A., & Birnboim, H. C. (1997). Receptor-mediated and protein kinase-dependent growth enhancement of primary human fibroblasts by platelet activating factor. Molecular Carcinogenesis, 20(4), 366–75.PubMedCrossRefGoogle Scholar
  24. 24.
    Roth, M., Nauck, M., Yousefi, S., Tamm, M., Blaser, K., Perruchoud, A. P., et al. (1996). Platelet-activating factor exerts mitogenic activity and stimulates expression of interleukin 6 and interleukin 8 in human lung fibroblasts via binding to its functional receptor. Journal of Experimental Medicine, 184(1), 191–01.PubMedCrossRefGoogle Scholar
  25. 25.
    Prescott, S. M., Zimmerman, G. A., Stafforini, D. M., & McIntyre, T. M. (2000). Platelet-activating factor and related lipid mediators. Annual Reviews of Biochemical, 69, 419–45.CrossRefGoogle Scholar
  26. 26.
    Camussi, G., Montrucchio, G., Lupia, E., De Martino, A., Perona, L., Arese, M., et al. (1995). Platelet-activating factor directly stimulates in vitro migration of endothelial cells and promotes in vivo angiogenesis by a heparin-dependent mechanism. Journal of Immunology, 154(12), 6492–501.Google Scholar
  27. 27.
    Robert, E. G., & Hunt, J. D. (2001). Lipid messengers as targets for antiangiogenic therapy. Current Pharmaceutical Design, 7(16), 1615–626.PubMedCrossRefGoogle Scholar
  28. 28.
    Bussolino, F., Arese, M., Montrucchio, G., Barra, L., Primo, L., Benelli, R., et al. (1995). Platelet activating factor produced in vitro by Kaposi’s sarcoma cells induces and sustains in vivo angiogenesis. Journal of Clinical Investigation, 96(2), 940–52.PubMedCrossRefGoogle Scholar
  29. 29.
    Shaw, J. O., Pinckard, R. N., Ferrigni, K. S., McManus, L. M., & Hanahan, D. J. (1981). Activation of human neutrophils with 1-O-hexadecyl/octadecyl-2-acetyl-snglycerol-3-phosphorylcholine (platelet activating factor). Journal of Immunology, 127(3), 1250–255.Google Scholar
  30. 30.
    Rola-Pleszczynski, M., Pouliot, C., Turcotte, S., Pignol, B., Braquet, P., & Bouvrette, L. (1988). Immune regulation by platelet-activating factor. I. Induction of suppressor cell activity in human monocytes and CD8+ T cells and of helper cell activity in CD4+ T cells. Journal of Immunology, 140(10), 3547–552.Google Scholar
  31. 31.
    Stafforini, D. M., McIntyre, T. M., Zimmerman, G. A., & Prescott, S. M. (2003). Platelet-activating factor, a pleiotrophic mediator of physiological and pathological processes. Critical Reviews in Clinical Laboratory Sciences, 40(6), 643–72.PubMedCrossRefGoogle Scholar
  32. 32.
    Travers, J. B. (1999). Oxidative stress can activate the epidermal platelet-activating factor receptor. Journal of Investigative Dermatology, 112(3), 279–83.PubMedCrossRefGoogle Scholar
  33. 33.
    Shimizu, T., Mutoh, H., & Kato, S. (1996). Platelet-activating factor receptor. Gene structure and tissue-specific regulation. Advances in Experimental Medicine and Biology, 416, 79–4.PubMedGoogle Scholar
  34. 34.
    Mutoh, H., Bito, H., Minami, M., Nakamura, M., Honda, Z., Izumi, T., et al. (1993). Two different promoters direct expression of two distinct forms of mRNAs of human platelet-activating factor receptor. FEBS Letters, 322(2), 129–34.PubMedCrossRefGoogle Scholar
  35. 35.
    Benveniste, J., Tence, M., Varenne, P., Bidault, J., Boullet, C., & Polonsky, J. (1979). [Semi-synthesis and proposed structure of platelet-activating factor (P.A.F.): PAF-acether an alkyl ether analog of lysophosphatidylcholine]. Comptes Rendus des Seances de Academie Sciences De Roumanie, 289(14), 1037–040.Google Scholar
  36. 36.
    Blank, M. L., Snyder, F., Byers, L. W., Brooks, B., & Muirhead, E. E. (1979). Antihypertensive activity of an alkyl ether analog of phosphatidylcholine. Biochemical and Biophysical Research Communications, 90(4), 1194–200.PubMedCrossRefGoogle Scholar
  37. 37.
    Demopoulos, C. A., Pinckard, R. N., & Hanahan, D. J. (1979). Platelet-activating factor. Evidence for 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine as the active component (a new class of lipid chemical mediators). Journal of Biological Chemistry, 254(19), 9355–358.PubMedGoogle Scholar
  38. 38.
    Benveniste, J., Henson, P. M., & Cochrane, C. G. (1972). Leukocyte-dependent histamine release from rabbit platelets. The role of IgE, basophils, and a platelet-activating factor. Journal of Experimental Medicine, 136(6), 1356–377.PubMedCrossRefGoogle Scholar
  39. 39.
    Snyder, F. (1995). Platelet-activating factor and its analogs: Metabolic pathways and related intracellular processes. Biochimica Biophysica Acta, 1254(3), 231–49.Google Scholar
  40. 40.
    Prescott, S. M., Zimmerman, G. A., & McIntyre, T. M. (1990). Platelet-activating factor. Journal of Biological Chemistry, 265(29), 17381–7384.PubMedGoogle Scholar
  41. 41.
    Serhan, C. N., Haeggstrom, J. Z., & Leslie, C. C. (1996). Lipid mediator networks in cell signaling: Update and impact of cytokines. FASEB Journal, 10(10), 1147–158.PubMedGoogle Scholar
  42. 42.
    Marathe, G. K., Davies, S. S., Harrison, K. A., Silva, A. R., Murphy, R. C., Castro-Faria-Neto, H., et al. (1999). Inflammatory platelet-activating factor-like phospholipids in oxidized low density lipoproteins are fragmented alkyl phosphatidylcholines. Journal of Biological Chemistry, 274(40), 28395–8404.PubMedCrossRefGoogle Scholar
  43. 43.
    Uemura, Y., Lee, T. C., & Snyder, F. (1991). A coenzyme A-independent transacylase is linked to the formation of platelet-activating factor (PAF) by generating the lyso-PAF intermediate in the remodeling pathway. Journal of Biological Chemistry, 266(13), 8268–272.PubMedGoogle Scholar
  44. 44.
    Montrucchio, G., Alloatti, G., & Camussi, G. (2000). Role of platelet-activating factor in cardiovascular pathophysiology. Physiological Reviews, 80(4), 1669–699.PubMedGoogle Scholar
  45. 45.
    Blank, M. L., Lee, Y. J., Cress, E. A., & Snyder, F. (1988). Stimulation of the de novo pathway for the biosynthesis of platelet-activating factor (PAF) via cytidylyltransferase activation in cells with minimal endogenous PAF production. Journal of Biological Chemistry, 263(12), 5656–661.PubMedGoogle Scholar
  46. 46.
    Shindou, H., Hishikawa, D., Nakanishi, H., Harayama, T., Ishii, S., Taguchi, R., et al. (2007). A single enzyme catalyzes both platelet-activating factor production and membrane biogenesis of inflammatory cells. Cloning and characterization of acetyl-CoA:LYSO-PAF acetyltransferase. Journal of Biological Chemistry, 282(9), 6532–539.PubMedCrossRefGoogle Scholar
  47. 47.
    Stafforini, D. M., Prescott, S. M., & McIntyre, T. M. (1987). Human plasma platelet-activating factor acetylhydrolase. Purification and properties. Journal of Biological Chemistry, 262(9), 4223–230.PubMedGoogle Scholar
  48. 48.
    Travers, J. B., Sprecher, H., & Fertel, R. H. (1990). The metabolism of platelet-activating factor in human T-lymphocytes. Biochimica et biophysica acta, 1042(2), 193–97.PubMedGoogle Scholar
  49. 49.
    Wilcox, R. W., Wykle, R. L., Schmitt, J. D., & Daniel, L. W. (1987). The degradation of platelet-activating factor and related lipids: Susceptibility to phospholipases C and D. Lipids, 22(11), 800–07.PubMedCrossRefGoogle Scholar
  50. 50.
    Bito, H., Honda, Z., Nakamura, M., & Shimizu, T. (1994). Cloning, expression and tissue distribution of rat platelet-activating-factor-receptor cDNA. European Journal of Biochemistry, 221(1), 211–18.PubMedCrossRefGoogle Scholar
  51. 51.
    Nakamura, M., Honda, Z., Izumi, T., Sakanaka, C., Mutoh, H., Minami, M., et al. (1991). Molecular cloning and expression of platelet-activating factor receptor from human leukocytes. Journal of Biological Chemistry, 266(30), 20400–0405.PubMedGoogle Scholar
  52. 52.
    Ye, R. D., Prossnitz, E. R., Zou, A. H., and Cochrane, C. G. (1991). Characterization of a human cDNA that encodes a functional receptor for platelet activating factor. Biochemical and Biophysical Research Communications, 180(1), 105–11.PubMedCrossRefGoogle Scholar
  53. 53.
    Ishii, S., Nagase, T., & Shimizu, T. (2002). Platelet-activating factor receptor. Prostaglandins Other Lipid Mediators 68–9, 599–09.CrossRefGoogle Scholar
  54. 54.
    Ishii, S., & Shimizu, T. (2000). Platelet-activating factor (PAF) receptor and genetically engineered PAF receptor mutant mice. Progress in Lipid Research, 39(1), 41–2.PubMedCrossRefGoogle Scholar
  55. 55.
    Nakamura, M., Honda, Z., Waga, I., Matsumoto, T., Noma, M., & Shimizu, T. (1992). Endotoxin transduces Ca2+ signaling via platelet-activating factor receptor. FEBS Letters, 314(2), 125–29.PubMedCrossRefGoogle Scholar
  56. 56.
    Uozumi, N., Kume, K., Nagase, T., Nakatani, N., Ishii, S., Tashiro, F., et al. (1997). Role of cytosolic phospholipase A2 in allergic response and parturition. Nature, 390(6660), 618–22.PubMedCrossRefGoogle Scholar
  57. 57.
    Fukunaga, K., Ishii, S., Asano, K., Yokomizo, T., Shiomi, T., Shimizu, T., et al. (2001). Single nucleotide polymorphism of human platelet-activating factor receptor impairs G-protein activation. Journal of Biological Chemistry, 276(46), 43025–3030.PubMedCrossRefGoogle Scholar
  58. 58.
    Dupre, D. J., Chen, Z., Le Gouill, C., Theriault, C., Parent, J. L., Rola-Pleszczynski, M., et al. (2003). Trafficking, ubiquitination, and down-regulation of the human platelet-activating factor receptor. Journal of Biological Chemistry, 278(48), 48228–8235.PubMedCrossRefGoogle Scholar
  59. 59.
    Ihida, K., Predescu, D., Czekay, R. P., & Palade, G. E. (1999). Platelet activating factor receptor (PAF-R) is found in a large endosomal compartment in human umbilical vein endothelial cells. Journal of Cell Science, 112(Pt 3), 285–95.PubMedGoogle Scholar
  60. 60.
    Marcheselli, V. L., Rossowska, M. J., Domingo, M. T., Braquet, P., & Bazan, N. G. (1990). Distinct platelet-activating factor binding sites in synaptic endings and in intracellular membranes of rat cerebral cortex. Journal of Biological Chemistry, 265(16), 9140–145.PubMedGoogle Scholar
  61. 61.
    Marrache, A. M., Gobeil, F., Jr., Bernier, S. G., Stankova, J., Rola-Pleszczynski, M., Choufani, S., et al. (2002). Proinflammatory gene induction by platelet-activating factor mediated via its cognate nuclear receptor. Journal of Immunology, 169(11), 6474–481.Google Scholar
  62. 62.
    Zhu, T., Gobeil, F., Vazquez-Tello, A., Leduc, M., Rihakova, L., Bossolasco, M., et al. (2006). Intracrine signaling through lipid mediators and their cognate nuclear G-protein-coupled receptors: A paradigm based on PGE2, PAF, and LPA1 receptors. Canadian Journal of Physiology and Pharmacology, 84(3–), 377–91.PubMedCrossRefGoogle Scholar
  63. 63.
    Chao, W., & Olson, M. S. (1993). Platelet-activating factor: Receptors and signal transduction. Biochemical Journal, 292(Pt 3), 617–29.PubMedGoogle Scholar
  64. 64.
    Franklin, R. A., Mazer, B., Sawami, H., Mills, G. B., Terada, N., Lucas, J. J., et al. (1993). Platelet-activating factor triggers the phosphorylation and activation of MAP-2 kinase and S6 peptide kinase activity in human B cell lines. Journal of Immunology, 151(4), 1802–810.Google Scholar
  65. 65.
    Honda, Z., Takano, T., Gotoh, Y., Nishida, E., Ito, K., & Shimizu, T. (1994). Transfected platelet-activating factor receptor activates mitogen-activated protein (MAP) kinase and MAP kinase kinase in Chinese hamster ovary cells. Journal of Biological Chemistry, 269(3), 2307–315.PubMedGoogle Scholar
  66. 66.
    Marques, S. A., Dy, L. C., Southall, M. D., Yi, Q., Smietana, E., Kapur, R., et al. (2002). The platelet-activating factor receptor activates the extracellular signal-regulated kinase mitogen-activated protein kinase and induces proliferation of epidermal cells through an epidermal growth factor-receptor-dependent pathway. Journal of Pharmacology and Experimental Therapeutics, 300(3), 1026–035.PubMedCrossRefGoogle Scholar
  67. 67.
    Landis, M., Yi, Q., Hyatt, A. M., Travers, A. R., Lewis, D. A., & Travers, J. B. (2007). Involvement of P38 MAP kinase in the augmentation of UVB-mediated apoptosis via the epidermal platelet-activating factor receptor. Archives of Dermatological Research, 299, 263–66.Google Scholar
  68. 68.
    Melnikova, V. O., Mourad-Zeidan, A. A., Lev, D. C., & Bar-Eli, M. (2006). Platelet-activating factor mediates MMP-2 expression and activation via phosphorylation of cAMP-response element-binding protein and contributes to melanoma metastasis. Journal of Biological Chemistry, 281(5), 2911–922.PubMedCrossRefGoogle Scholar
  69. 69.
    Nick, J. A., Avdi, N. J., Young, S. K., Knall, C., Gerwins, P., Johnson, G. L., et al. (1997). Common and distinct intracellular signaling pathways in human neutrophils utilized by platelet activating factor and FMLP. Journal of Clinical Investigation, 99(5), 975–86.PubMedCrossRefGoogle Scholar
  70. 70.
    Coffer, P. J., Schweizer, R. C., Dubois, G. R., Maikoe, T., Lammers, J. W., & Koenderman, L. (1998). Analysis of signal transduction pathways in human eosinophils activated by chemoattractants and the T-helper 2-derived cytokines interleukin-4 and interleukin-5. Blood, 91(7), 2547–557.PubMedGoogle Scholar
  71. 71.
    Kravchenko, V. V., Pan, Z., Han, J., Herbert, J. M., Ulevitch, R. J., & Ye, R. D. (1995). Platelet-activating factor induces NF-kappa B activation through a G protein-coupled pathway. Journal of Biological Chemistry, 270(25), 14928–4934.PubMedCrossRefGoogle Scholar
  72. 72.
    Deo, D. D., Axelrad, T. W., Robert, E. G., Marcheselli, V., Bazan, N. G., & Hunt, J. D. (2002). Phosphorylation of STAT-3 in response to basic fibroblast growth factor occurs through a mechanism involving platelet-activating factor, JAK-2, and Src in human umbilical vein endothelial cells. Evidence for a dual kinase mechanism. Journal of Biological Chemistry, 277(24), 21237–1245.PubMedCrossRefGoogle Scholar
  73. 73.
    Deo, D. D., Bazan, N. G., & Hunt, J. D. (2004). Activation of platelet-activating factor receptor-coupled G alpha q leads to stimulation of Src and focal adhesion kinase via two separate pathways in human umbilical vein endothelial cells. Journal of Biological Chemistry, 279(5), 3497–508.PubMedCrossRefGoogle Scholar
  74. 74.
    Kume, K., & Shimizu, T. (1997). Platelet-activating factor (PAF) induces growth stimulation, inhibition, and suppression of oncogenic transformation in NRK cells overexpressing the PAF receptor. Journal of Biological Chemistry, 272(36), 22898–2904.PubMedCrossRefGoogle Scholar
  75. 75.
    Axelrad, T. W., Deo, D. D., Ottino, P., Van Kirk, J., Bazan, N. G., Bazan, H. E., et al. (2004). Platelet-activating factor (PAF) induces activation of matrix metalloproteinase 2 activity and vascular endothelial cell invasion and migration. FASEB Journal, 18(3), 568–70.PubMedGoogle Scholar
  76. 76.
    Ko, H. M., Park, Y. M., Jung, B., Kim, H. A., Choi, J. H., Park, S. J., et al. (2005). Involvement of matrix metalloproteinase-9 in platelet-activating factor-induced angiogenesis. FEBS Letters, 579(11), 2369–375.PubMedCrossRefGoogle Scholar
  77. 77.
    Ottino, P., & Bazan, H. E. (2001). Corneal stimulation of MMP-1, -9 and uPA by platelet-activating factor is mediated by cyclooxygenase-2 metabolites. Current Eye Research, 23(2), 77–5.PubMedCrossRefGoogle Scholar
  78. 78.
    Ottino, P., He, J., Axelrad, T. W., & Bazan, H. E. (2005). PAF-induced furin and MT1-MMP expression is independent of MMP-2 activation in corneal myofibroblasts. Investigative Ophthalmology and Visual Science, 46(2), 487–96.PubMedCrossRefGoogle Scholar
  79. 79.
    Sugano, T., Nasu, K., Narahara, H., Kawano, Y., Nishida, Y., & Miyakawa, I. (2000). Platelet-activating factor induces an imbalance between matrix metalloproteinase-1 and tissue inhibitor of metalloproteinases-1 expression in human uterine cervical fibroblasts. Biology of Reproduction, 62(3), 540–46.PubMedCrossRefGoogle Scholar
  80. 80.
    Takafuji, S., Ishida, A., Miyakuni, Y., & Nakagawa, T. (2003). Matrix metalloproteinase-9 release from human leukocytes. Journal of Investigational Allergology & Clinical Immunology, 13(1), 50–5.Google Scholar
  81. 81.
    Barletta, E., Mugnai, G., & Ruggieri, S. (2002). Platelet activating factor inhibits the expression of matrix metalloproteinases and affects invasiveness and differentiation in a system of human neuroblastoma clones. Biological Chemistry, 383(1), 189–97.PubMedCrossRefGoogle Scholar
  82. 82.
    Brizzi, M. F., Battaglia, E., Montrucchio, G., Dentelli, P., Del Sorbo, L., Garbarino, G., et al. (1999) Thrombopoietin stimulates endothelial cell motility and neoangiogenesis by a platelet-activating factor-dependent mechanism. Circulation Research, 84(7), 785–96.PubMedGoogle Scholar
  83. 83.
    Camussi, G., Montrucchio, G., Lupia, E., Soldi, R., Comoglio, P. M., & Bussolino, F. (1997). Angiogenesis induced in vivo by hepatocyte growth factor is mediated by platelet-activating factor synthesis from macrophages. Journal of Immunology, 158(3), 1302–309.Google Scholar
  84. 84.
    Montrucchio, G., Lupia, E., Battaglia, E., Passerini, G., Bussolino, F., Emanuelli, G., et al. (1994). Tumor necrosis factor alpha-induced angiogenesis depends on in situ platelet-activating factor biosynthesis. Journal of Experimental Medicine, 180(1), 377–82.PubMedCrossRefGoogle Scholar
  85. 85.
    Montrucchio, G., Lupia, E., de Martino, A., Battaglia, E., Arese, M., Tizzani, A., et al. (1997). Nitric oxide mediates angiogenesis induced in vivo by platelet-activating factor and tumor necrosis factor-alpha. American Journal of Pathology, 151(2), 557–63.PubMedGoogle Scholar
  86. 86.
    Montrucchio, G., Sapino, A., Bussolati, B., Ghisolfi, G., Rizea-Savu, S., Silvestro, L., et al. (1998). Potential angiogenic role of platelet-activating factor in human breast cancer. American Journal of Pathology, 153(5), 1589–596.PubMedGoogle Scholar
  87. 87.
    Bussolati, B., Biancone, L., Cassoni, P., Russo, S., Rola-Pleszczynski, M., Montrucchio, G., et al. (2000). PAF produced by human breast cancer cells promotes migration and proliferation of tumor cells and neo-angiogenesis. American Journal of Pathology, 157(5), 1713–725.PubMedGoogle Scholar
  88. 88.
    Sirois, M. G., & Edelman, E. R. (1997). VEGF effect on vascular permeability is mediated by synthesis of platelet-activating factor. American Journal of Physiology, 272(6 Pt 2), H2746–756.PubMedGoogle Scholar
  89. 89.
    Rollin, S., Lemieux, C., Maliba, R., Favier, J., Villeneuve, L. R., Allen, B. G., et al. (2004). VEGF-mediated endothelial P-selectin translocation: Role of VEGF receptors and endogenous PAF synthesis. Blood, 103(10), 3789–797.PubMedCrossRefGoogle Scholar
  90. 90.
    Maliba, R., Lapointe, S., Neagoe, P. E., Brkovic, A., & Sirois, M. G. (2006). Angiopoietins-1 and -2 are both capable of mediating endothelial PAF synthesis: Intracellular signalling pathways. Cell Signal, 18(11), 1947–957.PubMedCrossRefGoogle Scholar
  91. 91.
    Russo, S., Bussolati, B., Deambrosis, I., Mariano, F., & Camussi, G. (2003). Platelet-activating factor mediates CD40-dependent angiogenesis and endothelial-smooth muscle cell interaction. Journal of Immunology, 171(10), 5489–497.Google Scholar
  92. 92.
    Seo, K. H., Lee, H. S., Jung, B., Ko, H. M., Choi, J. H., Park, S. J., et al. (2004). Estrogen enhances angiogenesis through a pathway involving platelet-activating factor-mediated nuclear factor-kappaB activation. Cancer Research, 64(18), 6482–488.PubMedCrossRefGoogle Scholar
  93. 93.
    Cellai, C., Laurenzana, A., Vannucchi, A. M., Caporale, R., Paglierani, M., Di Lollo, S., et al. (2006). Growth inhibition and differentiation of human breast cancer cells by the PAFR antagonist WEB-2086. British Journal of Cancer, 94(11), 1637–642.PubMedGoogle Scholar
  94. 94.
    Boccellino, M., Biancone, L., Cantaluppi, V., Ye, R. D., & Camussi, G. (2000). Effect of platelet-activating factor receptor expression on CHO cell motility. Journal of Cellular Physiology, 183(2), 254–64.PubMedCrossRefGoogle Scholar
  95. 95.
    Bussolati, B., Russo, S., Deambrosis, I., Cantaluppi, V., Volpe, A., Ferrando, U., et al. (2002). Expression of CD154 on renal cell carcinomas and effect on cell proliferation, motility and platelet-activating factor synthesis. International Journal of Cancer, 100(6), 654–61.CrossRefGoogle Scholar
  96. 96.
    Denizot, Y., Truffinet, V., Bouvier, S., Gainant, A., Cubertafond, P., & Mathonnet, M. (2004). Elevated plasma phospholipase A2 and platelet-activating factor acetylhydrolase activity in colorectal cancer. Mediators of Inflammation, 13(1), 53–4.PubMedCrossRefGoogle Scholar
  97. 97.
    Denizot, Y., Descottes, B., Truffinet, V., Valleix, D., Labrousse, F., & Mathonnet, M. (2005). Platelet-activating factor and liver metastasis of colorectal cancer. International Journal of Cancer, 113(3), 503–05.CrossRefGoogle Scholar
  98. 98.
    Denizot, Y., Gainant, A., Guglielmi, L., Bouvier, S., Cubertafond, P., & Mathonnet, M. (2003). Tissue concentrations of platelet-activating factor in colorectal carcinoma: Inverse relationships with Dukes–stage of patients. Oncogene, 22(46), 7222–224.PubMedCrossRefGoogle Scholar
  99. 99.
    Mathonnet, M., Descottes, B., Valleix, D., Truffinet, V., Labrousse, F., & Denizot, Y. (2006). Platelet-activating factor in cirrhotic liver and hepatocellular carcinoma. World Journal of Gastroenterology, 12(17), 2773–778.PubMedGoogle Scholar
  100. 100.
    Denizot, Y., Chianea, T., Labrousse, F., Truffinet, V., Delage, M., & Mathonnet, M. (2005). Platelet-activating factor and human thyroid cancer. European Journal of Endocrinology, 153(1), 31–0.PubMedCrossRefGoogle Scholar
  101. 101.
    Denizot, Y., De Armas, R., Caire, F., Pommepuy, I., Truffinet, V., & Labrousse, F. (2006). Platelet-activating factor and human meningiomas. Neuropathology & Applied Neurobiology 32(6), 674–78.CrossRefGoogle Scholar
  102. 102.
    Guglielmi, L., Trimoreau, F., Donnard, M., Jaccard, A., Bordessoule, D., & Denizot, Y. (2003). Presence of membrane platelet-activating factor receptors on B cells of chronic B cell leukaemia patients. Leukemia & Lymphoma, 44(6), 1087–088.CrossRefGoogle Scholar
  103. 103.
    Kotelevets, L., Noe, V., Bruyneel, E., Myssiakine, E., Chastre, E., Mareel, M., et al. (1998). Inhibition by platelet-activating factor of Src- and hepatocyte growth factor-dependent invasiveness of intestinal and kidney epithelial cells. Phosphatidylinositol 3–kinase is a critical mediator of tumor invasion. Journal of Biological Chemistry, 273(23), 14138–4145.PubMedCrossRefGoogle Scholar
  104. 104.
    Kita, Y., Takahashi, T., Uozumi, N., & Shimizu, T. (2005). A multiplex quantitation method for eicosanoids and platelet-activating factor using column-switching reversed-phase liquid chromatography-tandem mass spectrometry. Analytical Biochemistry, 342(1), 134–43.PubMedCrossRefGoogle Scholar
  105. 105.
    Im, S. Y., Ko, H. M., Kim, J. W., Lee, H. K., Ha, T. Y., Lee, H. B., et al. (1996). Augmentation of tumor metastasis by platelet-activating factor. Cancer Research, 56(11), 2662–665.PubMedGoogle Scholar
  106. 106.
    Sato, S., Kume, K., Ito, C., Ishii, S., & Shimizu, T. (1999). Accelerated proliferation of epidermal keratinocytes by the transgenic expression of the platelet-activating factor receptor. Archives of Dermatological Research, 291(11), 614–21.PubMedCrossRefGoogle Scholar
  107. 107.
    Ishii, S., Nagase, T., Tashiro, F., Ikuta, K., Sato, S., Waga, I., et al. (1997). Bronchial hyperreactivity, increased endotoxin lethality and melanocytic tumorigenesis in transgenic mice overexpressing platelet-activating factor receptor. EMBO Journal, 16(1), 133–42.PubMedCrossRefGoogle Scholar
  108. 108.
    Lee, J. T., & Herlyn, M. (2006). Microenvironmental influences in melanoma progression. Journal of Cellular Biochemistry. Google Scholar
  109. 109.
    Biancone, L., Cantaluppi, V., Del Sorbo, L., Russo, S., Tjoelker, L. W., & Camussi, G. (2003). Platelet-activating factor inactivation by local expression of platelet-activating factor acetyl-hydrolase modifies tumor vascularization and growth. Clinical Cancer Research, 9(11), 4214–220.PubMedGoogle Scholar
  110. 110.
    Fallani, A., Calorini, L., Mannini, A., Gabellieri, S., Mugnai, G., and Ruggieri, S. (2006). Platelet-activating factor (PAF) is the effector of IFN gamma-stimulated invasiveness and motility in a B16 melanoma line. Prostaglandins Other Lipid Mediators, 81(3–), 171–77.PubMedCrossRefGoogle Scholar
  111. 111.
    Ko, H. M., Kang, J. H., Jung, B., Kim, H. A., Park, S. J., Kim, K. J., et al. (2007). Critical role for matrix metalloproteinase-9 in platelet-activating factor-induced experimental tumor metastasis. International Journal of Cancer, 120(6), 1277–283.CrossRefGoogle Scholar
  112. 112.
    Mannori, G., Barletta, E., Mugnai, G., & Ruggieri, S. (2000). Interaction of tumor cells with vascular endothelia: Role of platelet-activating factor. Clinical & Experimental Metastasis, 18(1), 89–6.CrossRefGoogle Scholar
  113. 113.
    Barber, L. A., Spandau, D. F., Rathman, S. C., Murphy, R. C., Johnson, C. A., Kelley, S. W., et al. (1998). Expression of the platelet-activating factor receptor results in enhanced ultraviolet B radiation-induced apoptosis in a human epidermal cell line. Journal of Biological Chemistry, 273(30), 18891–8897.PubMedCrossRefGoogle Scholar
  114. 114.
    Sheng, Y., & Birkle, D. L. (1995). Release of platelet activating factor (PAF) and eicosanoids in UVC-irradiated corneal stromal cells. Current Eye Research, 14(5), 341–47.PubMedCrossRefGoogle Scholar
  115. 115.
    Calignano, A., Cirino, G., Meli, R., & Persico, P. (1988). Isolation and identification of platelet-activating factor in UV-irradiated guinea pig skin. Journal of Pharmacological Methods, 19(1), 89–1.PubMedCrossRefGoogle Scholar
  116. 116.
    Travers, J. B., Huff, J. C., Rola-Pleszczynski, M., Gelfand, E. W., Morelli, J. G., & Murphy, R. C. (1995). Identification of functional platelet-activating factor receptors on human keratinocytes. Journal of Investigative Dermatology, 105(6), 816–23.PubMedCrossRefGoogle Scholar
  117. 117.
    Pei, Y., Barber, L. A., Murphy, R. C., Johnson, C. A., Kelley, S. W., Dy, L. C., et al. (1998). Activation of the epidermal platelet-activating factor receptor results in cytokine and cyclooxygenase-2 biosynthesis. Journal of Immunology, 161(4), 1954–961.Google Scholar
  118. 118.
    Walterscheid, J. P., Ullrich, S. E., & Nghiem, D. X. (2002). Platelet-activating factor, a molecular sensor for cellular damage, activates systemic immune suppression. Journal of Experimental Medicine, 195(2), 171–79.PubMedCrossRefGoogle Scholar
  119. 119.
    De Fabo, E. C., Noonan, F. P., Fears, T., & Merlino, G. (2004). Ultraviolet B but not ultraviolet A radiation initiates melanoma. Cancer Research, 64(18), 6372–376.PubMedCrossRefGoogle Scholar
  120. 120.
    Noonan, F. P., Recio, J. A., Takayama, H., Duray, P., Anver, M. R., Rush, W. L., et al. (2001). Neonatal sunburn and melanoma in mice. Nature, 413(6853), 271–72.PubMedCrossRefGoogle Scholar
  121. 121.
    Marathe, G. K., Johnson, C., Billings, S. D., Southall, M. D., Pei, Y., Spandau, D., et al. (2005). Ultraviolet B radiation generates platelet-activating factor-like phospholipids underlying cutaneous damage. Journal of Biological Chemistry, 280(42), 35448–5457.PubMedCrossRefGoogle Scholar
  122. 122.
    Bennett, S. A., Leite, L. C., & Birnboim, H. C. (1993). Platelet activating factor, an endogenous mediator of inflammation, induces phenotypic transformation of rat embryo cells. Carcinogenesis, 14(7), 1289–296.PubMedCrossRefGoogle Scholar
  123. 123.
    Behrens, T. W., & Goodwin, J. S. (1990). Control of human T cell proliferation by platelet-activating factor. International Journal of Immunopharmacology, 12(2), 175–84.PubMedCrossRefGoogle Scholar
  124. 124.
    Maggi, M., Bonaccorsi, L., Finetti, G., Carloni, V., Muratori, M., Laffi, G., et al. (1994). Platelet-activating factor mediates an autocrine proliferative loop in the endometrial adenocarcinoma cell line HEC-1A. Cancer Research, 54(17), 4777–784.PubMedGoogle Scholar
  125. 125.
    Rutberg, S. E., Goldstein, I. M., Yang, Y. M., Stackpole, C. W., & Ronai, Z. (1994). Expression and transcriptional activity of AP-1, CRE, and URE binding proteins in B16 mouse melanoma subclones. Molecular Carcinogenesis, 10(2), 82–7.PubMedCrossRefGoogle Scholar
  126. 126.
    Bohm, M., Moellmann, G., Cheng, E., Alvarez-Franco, M., Wagner, S., Sassone-Corsi, P., et al. (1995). Identification of p90RSK as the probable CREB-Ser133 kinase in human melanocytes. Cell Growth & Differentiation, 6(3), 291–02.Google Scholar
  127. 127.
    Walton, K. M., Rehfuss, R. P., Chrivia, J. C., Lochner, J. E., & Goodman, R. H. (1992). A dominant repressor of cyclic adenosine 3–5–monophosphate (cAMP)-regulated enhancer-binding protein activity inhibits the cAMP-mediated induction of the somatostatin promoter in vivo. Molecular Endocrinology, 6(4), 647–55.PubMedCrossRefGoogle Scholar
  128. 128.
    Xie, S., Price, J. E., Luca, M., Jean, D., Ronai, Z., & Bar-Eli, M. (1997). Dominant-negative CREB inhibits tumor growth and metastasis of human melanoma cells. Oncogene, 15(17), 2069–075.PubMedCrossRefGoogle Scholar
  129. 129.
    Jean, D., Tellez, C., Huang, S., Davis, D. W., Bruns, C. J., McConkey, D. J., et al. (2000). Inhibition of tumor growth and metastasis of human melanoma by intracellular anti-ATF-1 single chain Fv fragment. Oncogene, 19(22), 2721–730.PubMedCrossRefGoogle Scholar
  130. 130.
    Jean, D., Harbison, M., McConkey, D. J., Ronai, Z., & Bar-Eli, M. (1998). CREB and its associated proteins act as survival factors for human melanoma cells. Journal of Biological Chemistry, 273(38), 24884–4890.PubMedCrossRefGoogle Scholar
  131. 131.
    Halaban, R., Ghosh, S., & Baird, A. (1987). bFGF is the putative natural growth factor for human melanocytes. In Vitro Cellular & Development Biology, 23(1), 47–2.CrossRefGoogle Scholar
  132. 132.
    Lev, D. C., Onn, A., Melinkova, V. O., Miller, C., Stone, V., Ruiz, M., et al. (2004). Exposure of melanoma cells to dacarbazine results in enhanced tumor growth and metastasis in vivo. Journal of Clinical Oncology, 22(11), 2092–100.PubMedCrossRefGoogle Scholar
  133. 133.
    Lev, D. C., Ruiz, M., Mills, L., McGary, E. C., Price, J. E., & Bar-Eli, M. (2003). Dacarbazine causes transcriptional up-regulation of interleukin 8 and vascular endothelial growth factor in melanoma cells: A possible escape mechanism from chemotherapy. Molecular Cancer Therapeutics, 2(8), 753–63.PubMedGoogle Scholar
  134. 134.
    Mandic, A., Viktorsson, K., Heiden, T., Hansson, J., & Shoshan, M. C. (2001). The MEK1 inhibitor PD98059 sensitizes C8161 melanoma cells to cisplatin-induced apoptosis. Melanoma Research, 11(1), 11–9.PubMedCrossRefGoogle Scholar
  135. 135.
    Huang, S., Mills, L., Mian, B., Tellez, C., McCarty, M., Yang, X. D., et al. (2002). Fully humanized neutralizing antibodies to interleukin-8 (ABX-IL8) inhibit angiogenesis, tumor growth, and metastasis of human melanoma. American Journal of Pathology, 161(1), 125–34.PubMedGoogle Scholar
  136. 136.
    Darst, M., Al-Hassani, M., Li, T., Yi, Q., Travers, J. M., Lewis, D. A., et al. (2004). Augmentation of chemotherapy-induced cytokine production by expression of the platelet-activating factor receptor in a human epithelial carcinoma cell line. Journal of Immunology, 172(10), 6330–335.Google Scholar
  137. 137.
    Southall, M. D., Isenberg, J. S., Nakshatri, H., Yi, Q., Pei, Y., Spandau, D. F., et al. (2001). The platelet-activating factor receptor protects epidermal cells from tumor necrosis factor (TNF) alpha and TNF-related apoptosis-inducing ligand-induced apoptosis through an NF-kappa B-dependent process. Journal of Biological Chemistry, 276(49), 45548–5554.PubMedCrossRefGoogle Scholar
  138. 138.
    Li, T., Southall, M. D., Yi, Q., Pei, Y., Lewis, D., Al-Hassani, M., et al. (2003). The epidermal platelet-activating factor receptor augments chemotherapy-induced apoptosis in human carcinoma cell lines. Journal of Biological Chemistry, 278(19), 16614–6621.PubMedCrossRefGoogle Scholar
  139. 139.
    Ma, X., & Bazan, H. E. (2001). Platelet-activating factor (PAF) enhances apoptosis induced by ultraviolet radiation in corneal epithelial cells through cytochrome c-caspase activation. Current Eye Research, 23(5), 326–35.PubMedCrossRefGoogle Scholar
  140. 140.
    Geromin, D., Bourge, J. F., Soulie, A., Pawliuk, R., Fleet, C., Michel, E., et al. (2004). Glycoprotein 170 induces platelet-activating factor receptor membrane expression and confers tumor cell hypersensitivity to NK-dependent cell lysis. Journal of Immunology, 172(6), 3604–611.Google Scholar
  141. 141.
    Thurnher, M., Zelle-Rieser, C., Ramoner, R., Bartsch, G., & Holtl, L. (2001). The disabled dendritic cell. FASEB Journal, 15(6), 1054–061.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  1. 1.Department of Cancer BiologyThe University of Texas M. D. Anderson Cancer CenterHoustonUSA

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