Cancer and Metastasis Reviews

, Volume 30, Issue 3–4, pp 295–309 | Cite as

Polyunsaturated fatty acid metabolism in prostate cancer

  • Isabelle M. Berquin
  • Iris J. Edwards
  • Steven J. Kridel
  • Yong Q. Chen


Polyunsaturated fatty acids (PUFA) play important roles in the normal physiology and in pathological states including inflammation and cancer. While much is known about the biosynthesis and biological activities of eicosanoids derived from ω6 PUFA, our understanding of the corresponding ω3 series lipid mediators is still rudimentary. The purpose of this review is not to offer a comprehensive summary of the literature on fatty acids in prostate cancer but rather to highlight some of the areas where key questions remain to be addressed. These include substrate preference and polymorphic variants of enzymes involved in the metabolism of PUFA, the relationship between de novo lipid synthesis and dietary lipid metabolism pathways, the contribution of cyclooxygenases and lipoxygenases as well as terminal synthases and prostanoid receptors in prostate cancer, and the potential role of PUFA in angiogenesis and cell surface receptor signaling.


Prostate cancer Polyunsaturated fatty acids Metabolism Cyclooxygenase Eicosanoids 


  1. 1.
    Calviello, G., Serini, S., & Piccioni, E. (2007). n-3 polyunsaturated fatty acids and the prevention of colorectal cancer: molecular mechanisms involved. Current Medicinal Chemistry, 14(29), 3059–3069.PubMedGoogle Scholar
  2. 2.
    Sun, H., Berquin, I. M., Owens, R. T., O’Flaherty, J. T., & Edwards, I. J. (2008). Peroxisome proliferator-activated receptor gamma-mediated up-regulation of syndecan-1 by n-3 fatty acids promotes apoptosis of human breast cancer cells. Cancer Research, 68(8), 2912–2919.PubMedGoogle Scholar
  3. 3.
    Berquin, I. M., Min, Y., Wu, R., et al. (2007). Modulation of prostate cancer genetic risk by omega-3 and omega-6 fatty acids. The Journal of Clinical Investigation, 117(7), 1866–1875.PubMedGoogle Scholar
  4. 4.
    Berquin, I. M., Edwards, I. J., & Chen, Y. Q. (2008). Multi-targeted therapy of cancer by omega-3 fatty acids. Cancer Letters, 269(2), 363–377.PubMedGoogle Scholar
  5. 5.
    Chen, Y. Q., Edwards, I. J., Kridel, S. J., Thornburg, T., & Berquin, I. M. (2007). Dietary fat–gene interactions in cancer. Cancer Metastasis Reviews, 26(3–4), 535–551.PubMedGoogle Scholar
  6. 6.
    Simopoulos, A. P. (2010). Genetic variants in the metabolism of omega-6 and omega-3 fatty acids: their role in the determination of nutritional requirements and chronic disease risk. Experimental Biology and Medicine, 235(7), 785–795.PubMedGoogle Scholar
  7. 7.
    Bernert, J. T., Jr., & Sprecher, H. (1975). Studies to determine the role rates of chain elongation and desaturation play in regulating the unsaturated fatty acid composition of rat liver lipids. Biochimica et Biophysica Acta, 398(3), 354–363.PubMedGoogle Scholar
  8. 8.
    Burdge, G. C., & Calder, P. C. (2005). Conversion of alpha-linolenic acid to longer-chain polyunsaturated fatty acids in human adults. Reproduction Nutrition Development, 45(5), 581–597.Google Scholar
  9. 9.
    Williams, C. M., & Burdge, G. (2006). Long-chain n-3 PUFA: plant v. marine sources. Proceedings of the Nutrition Society, 65(1), 42–50.PubMedGoogle Scholar
  10. 10.
    Pawlosky, R. J., Hibbeln, J. R., Novotny, J. A., & Salem, N., Jr. (2001). Physiological compartmental analysis of alpha-linolenic acid metabolism in adult humans. Journal of Lipid Research, 42(8), 1257–1265.PubMedGoogle Scholar
  11. 11.
    Portolesi, R., Powell, B. C., & Gibson, R. A. (2007). Competition between 24:5n-3 and ALA for Delta 6 desaturase may limit the accumulation of DHA in HepG2 cell membranes. Journal of Lipid Research, 48(7), 1592–1598.PubMedGoogle Scholar
  12. 12.
    Childs, C. E., Romeu-Nadal, M., Burdge, G. C., & Calder, P. C. (2008). Gender differences in the n-3 fatty acid content of tissues. Proceedings of the Nutrition Society, 67(1), 19–27.PubMedGoogle Scholar
  13. 13.
    Kitson, A. P., Stroud, C. K., & Stark, K. D. (2010). Elevated production of docosahexaenoic acid in females: potential molecular mechanisms. Lipids, 45(3), 209–224.PubMedGoogle Scholar
  14. 14.
    Bar, M., Wyman, S. K., Fritz, B. R., et al. (2008). MicroRNA discovery and profiling in human embryonic stem cells by deep sequencing of small RNA libraries. Stem Cells, 26(10), 2496–2505.PubMedGoogle Scholar
  15. 15.
    Nygaard, S., Jacobsen, A., Lindow, M., et al. (2009). Identification and analysis of miRNAs in human breast cancer and teratoma samples using deep sequencing. BMC Medical Genomics, 2, 35.PubMedGoogle Scholar
  16. 16.
    Creighton, C. J., Benham, A. L., Zhu, H., et al. (2010). Discovery of novel microRNAs in female reproductive tract using next generation sequencing. PLoS One, 5(3), e9637.PubMedGoogle Scholar
  17. 17.
    Schaeffer, L., Gohlke, H., Muller, M., et al. (2006). Common genetic variants of the FADS1 FADS2 gene cluster and their reconstructed haplotypes are associated with the fatty acid composition in phospholipids. Human Molecular Genetics, 15(11), 1745–1756.PubMedGoogle Scholar
  18. 18.
    Xie, L., & Innis, S. M. (2008). Genetic variants of the FADS1 FADS2 gene cluster are associated with altered (n-6) and (n-3) essential fatty acids in plasma and erythrocyte phospholipids in women during pregnancy and in breast milk during lactation. Journal of Nutrition, 138(11), 2222–2228.PubMedGoogle Scholar
  19. 19.
    Martinelli, N., Girelli, D., Malerba, G., et al. (2008). FADS genotypes and desaturase activity estimated by the ratio of arachidonic acid to linoleic acid are associated with inflammation and coronary artery disease. American Journal of Clinical Nutrition, 88(4), 941–949.PubMedGoogle Scholar
  20. 20.
    Malerba, G., Schaeffer, L., Xumerle, L., et al. (2008). SNPs of the FADS gene cluster are associated with polyunsaturated fatty acids in a cohort of patients with cardiovascular disease. Lipids, 43(4), 289–299.PubMedGoogle Scholar
  21. 21.
    Rzehak, P., Heinrich, J., Klopp, N., et al. (2009). Evidence for an association between genetic variants of the fatty acid desaturase 1 fatty acid desaturase 2 (FADS1 FADS2) gene cluster and the fatty acid composition of erythrocyte membranes. British Journal of Nutrition, 101(1), 20–26.PubMedGoogle Scholar
  22. 22.
    Bokor, S., Dumont, J., Spinneker, A., et al. (2010). Single nucleotide polymorphisms in the FADS gene cluster are associated with delta-5 and delta-6 desaturase activities estimated by serum fatty acid ratios. Journal of Lipid Research, 51(8), 2325–2333.PubMedGoogle Scholar
  23. 23.
    Lu, Y., Feskens, E. J., Dolle, M. E., et al. (2010). Dietary n-3 and n-6 polyunsaturated fatty acid intake interacts with FADS1 genetic variation to affect total and HDL-cholesterol concentrations in the Doetinchem Cohort Study. American Journal of Clinical Nutrition, 92(1), 258–265.PubMedGoogle Scholar
  24. 24.
    Mathias, R. A., Vergara, C., Gao, L., et al. (2010). FADS genetic variants and omega-6 polyunsaturated fatty acid metabolism in a homogeneous island population. Journal of Lipid Research, 51(9), 2766–2774.PubMedGoogle Scholar
  25. 25.
    Molto-Puigmarti, C., Plat, J., Mensink, R. P., et al. (2010). FADS1 FADS2 gene variants modify the association between fish intake and the docosahexaenoic acid proportions in human milk. American Journal of Clinical Nutrition, 91(5), 1368–1376.PubMedGoogle Scholar
  26. 26.
    Zietemann, V., Kroger, J., Enzenbach, C., et al. (2010). Genetic variation of the FADS1 FADS2 gene cluster and n-6 PUFA composition in erythrocyte membranes in the European Prospective Investigation into Cancer and Nutrition-Potsdam study. British Journal of Nutrition, 104(12), 1748–1759.PubMedGoogle Scholar
  27. 27.
    Koletzko, B., Lattka, E., Zeilinger, S., Illig, T., & Steer, C. (2011). Genetic variants of the fatty acid desaturase gene cluster predict amounts of red blood cell docosahexaenoic and other polyunsaturated fatty acids in pregnant women: findings from the Avon Longitudinal Study of Parents and Children. American Journal of Clinical Nutrition, 93(1), 211–219.PubMedGoogle Scholar
  28. 28.
    Kwak, J. H., Paik, J. K., Kim, O. Y., et al. (2011). FADS gene polymorphisms in Koreans: association with omega6 polyunsaturated fatty acids in serum phospholipids, lipid peroxides, and coronary artery disease. Atherosclerosis, 214(1), 94–100.PubMedGoogle Scholar
  29. 29.
    Tanaka, T., Shen, J., Abecasis, G. R., et al. (2009). Genome-wide association study of plasma polyunsaturated fatty acids in the InCHIANTI Study. PLoS Genetics, 5(1), e1000338.PubMedGoogle Scholar
  30. 30.
    Lattka, E., Illig, T., Heinrich, J., & Koletzko, B. (2009). FADS gene cluster polymorphisms: important modulators of fatty acid levels and their impact on atopic diseases. Journal of Nutrigenetics and Nutrigenomics, 2(3), 119–128.PubMedGoogle Scholar
  31. 31.
    Lattka, E., Illig, T., Heinrich, J., & Koletzko, B. (2010). Do FADS genotypes enhance our knowledge about fatty acid related phenotypes? Clinical Nutrition, 29(3), 277–287.PubMedGoogle Scholar
  32. 32.
    Martinelli, N., Consoli, L., & Olivieri, O. (2009). A ‘desaturase hypothesis’ for atherosclerosis: Janus-faced enzymes in omega-6 and omega-3 polyunsaturated fatty acid metabolism. Journal of Nutrigenetics and Nutrigenomics, 2(3), 129–139.PubMedGoogle Scholar
  33. 33.
    Lattka, E., Illig, T., Koletzko, B., & Heinrich, J. (2010). Genetic variants of the FADS1 FADS2 gene cluster as related to essential fatty acid metabolism. Current Opinion in Lipidology, 21(1), 64–69.PubMedGoogle Scholar
  34. 34.
    Merino, D. M., Ma, D. W., & Mutch, D. M. (2010). Genetic variation in lipid desaturases and its impact on the development of human disease. Lipids in Health and Disease, 9, 63.PubMedGoogle Scholar
  35. 35.
    Merino, D. M., Johnston, H., Clarke, S., et al. (2011). Polymorphisms in FADS1 and FADS2 alter desaturase activity in young Caucasian and Asian adults. Molecular Genetics and Metabolism, 103(2), 171–178.PubMedGoogle Scholar
  36. 36.
    Kuhajda, F. P. (2006). Fatty acid synthase and cancer: new application of an old pathway. Cancer Research, 66(12), 5977–5980.PubMedGoogle Scholar
  37. 37.
    Menendez, J. A., & Lupu, R. (2007). Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis. Nature Reviews. Cancer, 7(10), 763–777.PubMedGoogle Scholar
  38. 38.
    Bandyopadhyay, S., Pai, S. K., Watabe, M., et al. (2005). FAS expression inversely correlates with PTEN level in prostate cancer and a PI 3-kinase inhibitor synergizes with FAS siRNA to induce apoptosis. Oncogene, 24(34), 5389–5395.PubMedGoogle Scholar
  39. 39.
    Milgraum, L. Z., Witters, L. A., Pasternack, G. R., & Kuhajda, F. P. (1997). Enzymes of the fatty acid synthesis pathway are highly expressed in in situ breast carcinoma. Clinical Cancer Research, 3(11), 2115–2120.PubMedGoogle Scholar
  40. 40.
    Pflug, B. R., Pecher, S. M., Brink, A. W., Nelson, J. B., & Foster, B. A. (2003). Increased fatty acid synthase expression and activity during progression of prostate cancer in the TRAMP model. Prostate, 57(3), 245–254.PubMedGoogle Scholar
  41. 41.
    Rossi, S., Graner, E., Febbo, P., et al. (2003). Fatty acid synthase expression defines distinct molecular signatures in prostate cancer. Molecular Cancer Research, 1(10), 707–715.PubMedGoogle Scholar
  42. 42.
    Shah, U. S., Dhir, R., Gollin, S. M., et al. (2006). Fatty acid synthase gene overexpression and copy number gain in prostate adenocarcinoma. Human Pathology, 37(4), 401–409.PubMedGoogle Scholar
  43. 43.
    Kridel, S. J., Lowther, W. T., & Pemble, C. Wt. (2007). Fatty acid synthase inhibitors: new directions for oncology. Expert Opin Investig Drugs, 16(11), 1817–1829.PubMedGoogle Scholar
  44. 44.
    Swinnen, J. V., Esquenet, M., Goossens, K., Heyns, W., & Verhoeven, G. (1997). Androgens stimulate fatty acid synthase in the human prostate cancer cell line LNCaP. Cancer Research, 57(6), 1086–1090.PubMedGoogle Scholar
  45. 45.
    Swinnen, J. V., Ulrix, W., Heyns, W., & Verhoeven, G. (1997). Coordinate regulation of lipogenic gene expression by androgens: evidence for a cascade mechanism involving sterol regulatory element binding proteins. Proceedings of the National Academy of Sciences of the United States of America, 94(24), 12975–12980.PubMedGoogle Scholar
  46. 46.
    Swinnen, J. V., & Verhoeven, G. (1998). Androgens and the control of lipid metabolism in human prostate cancer cells. The Journal of Steroid Biochemistry and Molecular Biology, 65(1–6), 191–198.PubMedGoogle Scholar
  47. 47.
    Swinnen, J. V., Roskams, T., Joniau, S., et al. (2002). Overexpression of fatty acid synthase is an early and common event in the development of prostate cancer. International Journal of Cancer, 98(1), 19–22.Google Scholar
  48. 48.
    Van de Sande, T., De Schrijver, E., Heyns, W., Verhoeven, G., & Swinnen, J. V. (2002). Role of the phosphatidylinositol 3′-kinase/PTEN/Akt kinase pathway in the overexpression of fatty acid synthase in LNCaP prostate cancer cells. Cancer Research, 62(3), 642–646.PubMedGoogle Scholar
  49. 49.
    Migita, T., Ruiz, S., Fornari, A., et al. (2009). Fatty acid synthase: a metabolic enzyme and candidate oncogene in prostate cancer. Journal of the National Cancer Institute, 101(7), 519–532.PubMedGoogle Scholar
  50. 50.
    Bauer, D. E., Hatzivassiliou, G., Zhao, F., Andreadis, C., & Thompson, C. B. (2005). ATP citrate lyase is an important component of cell growth and transformation. Oncogene, 24(41), 6314–6322.PubMedGoogle Scholar
  51. 51.
    Hatzivassiliou, G., Zhao, F., Bauer, D. E., et al. (2005). ATP citrate lyase inhibition can suppress tumor cell growth. Cancer Cell, 8(4), 311–321.PubMedGoogle Scholar
  52. 52.
    DeBerardinis, R. J., Mancuso, A., Daikhin, E., et al. (2007). Beyond aerobic glycolysis: transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis. Proceedings of the National Academy of Sciences, 104(49), 19345–19350.Google Scholar
  53. 53.
    Abu-Elheiga, L., Matzuk, M. M., Kordari, P., et al. (2005). Mutant mice lacking acetyl-CoA carboxylase 1 are embryonically lethal. PNAS, 102(34), 12011–12016.PubMedGoogle Scholar
  54. 54.
    Mao, J., DeMayo, F. J., Li, H., et al. (2006). Liver-specific deletion of acetyl-CoA carboxylase 1 reduces hepatic triglyceride accumulation without affecting glucose homeostasis. Proceedings of the National Academy of Sciences of the United States of America, 103(22), 8552–8557.PubMedGoogle Scholar
  55. 55.
    Chirala, S. S., Chang, H., Matzuk, M., et al. (2003). Fatty acid synthesis is essential in embryonic development: fatty acid synthase null mutants and most of the heterozygotes die in utero. Proceedings of the National Academy of Sciences of the United States of America, 100(11), 6358–6363.PubMedGoogle Scholar
  56. 56.
    Wakil, S. J. (1989). Fatty acid synthase, a proficient multifunctional enzyme. Biochemistry, 28(11), 4523–4530.PubMedGoogle Scholar
  57. 57.
    Wakil, S. J., Stoops, J. K., & Joshi, V. C. (1983). Fatty acid synthesis and its regulation. Annual Review of Biochemistry, 52(1), 537–579.PubMedGoogle Scholar
  58. 58.
    Smith, S. (1994). The animal fatty acid synthase: one gene, one polypeptide, seven enzymes. The FASEB Journal, 8(15), 1248–1259.PubMedGoogle Scholar
  59. 59.
    Chajes, V., Cambot, M., Moreau, K., Lenoir, G. M., & Joulin, V. (2006). Acetyl-CoA carboxylase alpha is essential to breast cancer cell survival. Cancer Research, 66(10), 5287–5294.PubMedGoogle Scholar
  60. 60.
    Knowles, L. M., Axelrod, F., Browne, C. D., & Smith, J. W. (2004). A fatty acid synthase blockade induces tumor cell-cycle arrest by down-regulating Skp2. Journal of Biological Chemistry, 279(29), 30540–30545.PubMedGoogle Scholar
  61. 61.
    Little, J. L., Wheeler, F. B., Fels, D. R., Koumenis, C., & Kridel, S. J. (2007). Inhibition of fatty acid synthase induces endoplasmic reticulum stress in tumor cells. Cancer Research, 67(3), 1262–1269.PubMedGoogle Scholar
  62. 62.
    Heiligtag, S. J., Bredehorst, R., & David, K. A. (2002). Key role of mitochondria in cerulenin-mediated apoptosis. Cell Death and Differentiation, 9(9), 1017–1025.PubMedGoogle Scholar
  63. 63.
    Fiorentino, M., Zadra, G., Palescandolo, E., et al. (2008). Overexpression of fatty acid synthase is associated with palmitoylation of Wnt1 and cytoplasmic stabilization of beta-catenin in prostate cancer. Laboratory Investigation, 88(12), 1340–1348.PubMedGoogle Scholar
  64. 64.
    Migita, T., Narita, T., Nomura, K., et al. (2008). ATP citrate lyase: activation and therapeutic implications in non-small cell lung cancer. Cancer Research, 68(20), 8547–8554.PubMedGoogle Scholar
  65. 65.
    Brusselmans, K., De Schrijver, E., Verhoeven, G., & Swinnen, J. V. (2005). RNA interference-mediated silencing of the acetyl-CoA-carboxylase-alpha gene induces growth inhibition and apoptosis of prostate cancer cells. Cancer Research, 65(15), 6719–6725.PubMedGoogle Scholar
  66. 66.
    Kridel, S. J., Axelrod, F., Rozenkrantz, N., & Smith, J. W. (2004). Orlistat is a novel inhibitor of fatty acid synthase with antitumor activity. Cancer Research, 64(6), 2070–2075.PubMedGoogle Scholar
  67. 67.
    Alli, P. M., Pinn, M. L., Jaffee, E. M., McFadden, J. M., & Kuhajda, F. P. (2005). Fatty acid synthase inhibitors are chemopreventive for mammary cancer in neu-N transgenic mice. Oncogene, 24(1), 39–46.PubMedGoogle Scholar
  68. 68.
    Kuhajda, F. P., Jenner, K., Wood, F. D., et al. (1994). Fatty acid synthesis: a potential selective target for antineoplastic therapy. Proceedings of the National Academy of Sciences of the United States of America, 91(14), 6379–6383.PubMedGoogle Scholar
  69. 69.
    Orita, H., Coulter, J., Tully, E., Kuhajda, F. P., & Gabrielson, E. (2008). Inhibiting fatty acid synthase for chemoprevention of chemically induced lung tumors. Clinical Cancer Research, 14(8), 2458–2464.PubMedGoogle Scholar
  70. 70.
    Swinnen, J. V., Van Veldhoven, P. P., Timmermans, L., et al. (2003). Fatty acid synthase drives the synthesis of phospholipids partitioning into detergent-resistant membrane microdomains. Biochemical and Biophysical Research Communications, 302(4), 898–903.PubMedGoogle Scholar
  71. 71.
    Rysman, E., Brusselmans, K., Scheys, K., et al. (2010). De novo lipogenesis protects cancer cells from free radicals and chemotherapeutics by promoting membrane lipid saturation. Cancer Research, 70(20), 8117–8126.PubMedGoogle Scholar
  72. 72.
    Chakravarthy, M. V., Pan, Z., Zhu, Y., et al. (2005). “New” hepatic fat activates PPAR[alpha] to maintain glucose, lipid, and cholesterol homeostasis. Cell Metabolism, 1(5), 309–322.PubMedGoogle Scholar
  73. 73.
    Chakravarthy, M. V., Lodhi, I. J., Yin, L., et al. (2009). Identification of a physiologically relevant endogenous ligand for PPAR[alpha] in liver. Cell, 138(3), 476–488.PubMedGoogle Scholar
  74. 74.
    De Schrijver, E., Brusselmans, K., Heyns, W., Verhoeven, G., & Swinnen, J. V. (2003). RNA interference-mediated silencing of the fatty acid synthase gene attenuates growth and induces morphological changes and apoptosis of LNCaP prostate cancer cells. Cancer Research, 63(13), 3799–3804.PubMedGoogle Scholar
  75. 75.
    Kuemmerle, N. B., Rysman, E., Lombardo, P. S., et al. (2011). Lipoprotein lipase links dietary fat to solid tumor cell proliferation. Molecular Cancer Therapeutics, 10(3), 427–436.PubMedGoogle Scholar
  76. 76.
    Simopoulos, A. P. (1999). Essential fatty acids in health and chronic disease. American Journal of Clinical Nutrition, 70(3 Suppl), 560S–569S.PubMedGoogle Scholar
  77. 77.
    Crawford, M. A., Casperd, N. M., & Sinclair, A. J. (1976). The long chain metabolites of linoleic avid linolenic acids in liver and brain in herbivores and carnivores. Comparative Biochemistry and Physiology. B, 54(3), 395–401.Google Scholar
  78. 78.
    Horrobin, D. F., Huang, Y. S., Cunnane, S. C., & Manku, M. S. (1984). Essential fatty acids in plasma, red blood cells and liver phospholipids in common laboratory animals as compared to humans. Lipids, 19(10), 806–811.PubMedGoogle Scholar
  79. 79.
    Fu, Z., & Sinclair, A. J. (2000). Increased alpha-linolenic acid intake increases tissue alpha-linolenic acid content and apparent oxidation with little effect on tissue docosahexaenoic acid in the guinea pig. Lipids, 35(4), 395–400.PubMedGoogle Scholar
  80. 80.
    Leyton, J., Drury, P. J., & Crawford, M. A. (1987). Differential oxidation of saturated and unsaturated fatty acids in vivo in the rat. British Journal of Nutrition, 57(3), 383–393.PubMedGoogle Scholar
  81. 81.
    DeLany, J. P., Windhauser, M. M., Champagne, C. M., & Bray, G. A. (2000). Differential oxidation of individual dietary fatty acids in humans. American Journal of Clinical Nutrition, 72(4), 905–911.PubMedGoogle Scholar
  82. 82.
    Gavino, V. C., Cordeau, S., & Gavino, G. (2003). Kinetic analysis of the selectivity of acylcarnitine synthesis in rat mitochondria. Lipids, 38(4), 485–490.PubMedGoogle Scholar
  83. 83.
    Bryan, D. L., Hart, P., Forsyth, K., & Gibson, R. (2001). Incorporation of alpha-linolenic acid and linoleic acid into human respiratory epithelial cell lines. Lipids, 36(7), 713–717.PubMedGoogle Scholar
  84. 84.
    Martin-Chouly, C. A., Menier, V., Hichami, A., et al. (2000). Modulation of PAF production by incorporation of arachidonic acid and eicosapentaenoic acid in phospholipids of human leukemic monocyte-like cells THP-1. Prostaglandins & Other Lipid Mediators, 60(4–6), 127–135.Google Scholar
  85. 85.
    Pickett, W. C., & Ramesha, C. S. (1987). Ether phospholipids in control and 20:4-depleted rat PMN: additional evidence for a 1-O-alkyl-2-20:4-sn-glycerol-3-phosphocholine specific phospholipase A2. Agents and Actions, 21(3–4), 390–392.PubMedGoogle Scholar
  86. 86.
    Strokin, M., Sergeeva, M., & Reiser, G. (2003). Docosahexaenoic acid and arachidonic acid release in rat brain astrocytes is mediated by two separate isoforms of phospholipase A2 and is differently regulated by cyclic AMP and Ca2+. British Journal of Pharmacology, 139(5), 1014–1022.PubMedGoogle Scholar
  87. 87.
    Nakanishi, M., & Rosenberg, D. W. (2006). Roles of cPLA2alpha and arachidonic acid in cancer. Biochimica et Biophysica Acta, 1761(11), 1335–1343.PubMedGoogle Scholar
  88. 88.
    Murakami, M., Taketomi, Y., Girard, C., Yamamoto, K., & Lambeau, G. (2010). Emerging roles of secreted phospholipase A2 enzymes: lessons from transgenic and knockout mice. Biochimie, 92(6), 561–582.PubMedGoogle Scholar
  89. 89.
    Scott, K. F., Sajinovic, M., Hein, J., et al. (2010). Emerging roles for phospholipase A2 enzymes in cancer. Biochimie, 92(6), 601–610.PubMedGoogle Scholar
  90. 90.
    Dong, Q., Patel, M., Scott, K. F., Graham, G. G., Russell, P. J., & Sved, P. (2006). Oncogenic action of phospholipase A2 in prostate cancer. Cancer Letters, 240(1), 9–16.PubMedGoogle Scholar
  91. 91.
    Mirtti, T., Laine, V. J., Hiekkanen, H., et al. (2009). Group IIA phospholipase A as a prognostic marker in prostate cancer: relevance to clinicopathological variables and disease-specific mortality. APMIS, 117(3), 151–161.PubMedGoogle Scholar
  92. 92.
    Wang, D., & Dubois, R. N. (2010). Eicosanoids and cancer. Nature Reviews Cancer, 10(3), 181–193.PubMedGoogle Scholar
  93. 93.
    Panigrahy, D., Kaipainen, A., Greene, E. R., & Huang, S. (2010). Cytochrome P450-derived eicosanoids: the neglected pathway in cancer. Cancer Metastasis Reviews, 29(4), 723–735.PubMedGoogle Scholar
  94. 94.
    Chapkin, R. S., Kim, W., Lupton, J. R., & McMurray, D. N. (2009). Dietary docosahexaenoic and eicosapentaenoic acid: emerging mediators of inflammation. Prostaglandins, Leukotrienes, and Essential Fatty Acids, 81(2–3), 187–191.PubMedGoogle Scholar
  95. 95.
    Dubois, R. N., Abramson, S. B., Crofford, L., et al. (1998). Cyclooxygenase in biology and disease. The FASEB Journal, 12(12), 1063–1073.PubMedGoogle Scholar
  96. 96.
    Sobolewski, C., Cerella, C., Dicato, M., Ghibelli, L., & Diederich, M. (2010). The role of cyclooxygenase-2 in cell proliferation and cell death in human malignancies. Int J Cell Biol, 2010, 215158.PubMedGoogle Scholar
  97. 97.
    Wang, M. T., Honn, K. V., & Nie, D. (2007). Cyclooxygenases, prostanoids, and tumor progression. Cancer Metastasis Reviews, 26(3–4), 525–534.PubMedGoogle Scholar
  98. 98.
    Reese, A. C., Fradet, V., & Witte, J. S. (2009). Omega-3 fatty acids, genetic variants in COX-2 and prostate cancer. Journal of Nutrigenetics and Nutrigenomics, 2(3), 149–158.PubMedGoogle Scholar
  99. 99.
    Menter, D. G., Schilsky, R. L., & DuBois, R. N. (2010). Cyclooxygenase-2 and cancer treatment: understanding the risk should be worth the reward. Clinical Cancer Research, 16(5), 1384–1390.PubMedGoogle Scholar
  100. 100.
    Brash, A. R. (1999). Lipoxygenases: occurrence, functions, catalysis, and acquisition of substrate. Journal of Biological Chemistry, 274(34), 23679–23682.PubMedGoogle Scholar
  101. 101.
    Pidgeon, G. P., Lysaght, J., Krishnamoorthy, S., et al. (2007). Lipoxygenase metabolism: roles in tumor progression and survival. Cancer Metastasis Reviews, 26(3–4), 503–524.PubMedGoogle Scholar
  102. 102.
    Avis, I. M., Jett, M., Boyle, T., et al. (1996). Growth control of lung cancer by interruption of 5-lipoxygenase-mediated growth factor signaling. The Journal of Clinical Investigation, 97(3), 806–813.PubMedGoogle Scholar
  103. 103.
    Soumaoro, L. T., Iida, S., Uetake, H., et al. (2006). Expression of 5-lipoxygenase in human colorectal cancer. World Journal of Gastroenterology, 12(39), 6355–6360.PubMedGoogle Scholar
  104. 104.
    Ye, Y. N., Wu, W. K., Shin, V. Y., Bruce, I. C., Wong, B. C., & Cho, C. H. (2005). Dual inhibition of 5-LOX and COX-2 suppresses colon cancer formation promoted by cigarette smoke. Carcinogenesis, 26(4), 827–834.PubMedGoogle Scholar
  105. 105.
    Faronato, M., Muzzonigro, G., Milanese, G., et al. (2007). Increased expression of 5-lipoxygenase is common in clear cell renal cell carcinoma. Histology and Histopathology, 22(10), 1109–1118.PubMedGoogle Scholar
  106. 106.
    Hayashi, T., Nishiyama, K., & Shirahama, T. (2006). Inhibition of 5-lipoxygenase pathway suppresses the growth of bladder cancer cells. International Journal of Urology, 13(8), 1086–1091.PubMedGoogle Scholar
  107. 107.
    Ghosh, J. (2003). Inhibition of arachidonate 5-lipoxygenase triggers prostate cancer cell death through rapid activation of c-Jun N-terminal kinase. Biochemical and Biophysical Research Communications, 307(2), 342–349.PubMedGoogle Scholar
  108. 108.
    Ghosh, J., & Myers, C. E. (1998). Inhibition of arachidonate 5-lipoxygenase triggers massive apoptosis in human prostate cancer cells. Proceedings of the National Academy of Sciences of the United States of America, 95(22), 13182–13187.PubMedGoogle Scholar
  109. 109.
    Sharma, B. K., Pilania, P., & Singh, P. (2009). Modeling of cyclooxygenase-2 and 5-lipooxygenase inhibitory activity of apoptosis-inducing agents potentially useful in prostate cancer chemotherapy: derivatives of diarylpyrazole. Journal of Enzyme Inhibition and Medicinal Chemistry, 24(2), 607–615.PubMedGoogle Scholar
  110. 110.
    Sundaram, S., & Ghosh, J. (2006). Expression of 5-oxoETE receptor in prostate cancer cells: critical role in survival. Biochemical and Biophysical Research Communications, 339(1), 93–98.PubMedGoogle Scholar
  111. 111.
    Koh, W. P., Yuan, J. M., van den Berg, D., Lee, H. P., & Yu, M. C. (2004). Interaction between cyclooxygenase-2 gene polymorphism and dietary n-6 polyunsaturated fatty acids on colon cancer risk: the Singapore Chinese Health Study. British Journal of Cancer, 90(9), 1760–1764.PubMedGoogle Scholar
  112. 112.
    Siezen, C. L., van Leeuwen, A. I., Kram, N. R., Luken, M. E., van Kranen, H. J., & Kampman, E. (2005). Colorectal adenoma risk is modified by the interplay between polymorphisms in arachidonic acid pathway genes and fish consumption. Carcinogenesis, 26(2), 449–457.PubMedGoogle Scholar
  113. 113.
    Hedelin, M., Chang, E. T., Wiklund, F., et al. (2007). Association of frequent consumption of fatty fish with prostate cancer risk is modified by COX-2 polymorphism. International Journal of Cancer, 120(2), 398–405.Google Scholar
  114. 114.
    Fradet, V., Cheng, I., Casey, G., & Witte, J. S. (2009). Dietary omega-3 fatty acids, cyclooxygenase-2 genetic variation, and aggressive prostate cancer risk. Clinical Cancer Research, 15(7), 2559–2566.PubMedGoogle Scholar
  115. 115.
    Larsson, S. C., Kumlin, M., Ingelman-Sundberg, M., & Wolk, A. (2004). Dietary long-chain n-3 fatty acids for the prevention of cancer: a review of potential mechanisms. American Journal of Clinical Nutrition, 79(6), 935–945.PubMedGoogle Scholar
  116. 116.
    Haeggstrom, J. Z., Rinaldo-Matthis, A., Wheelock, C. E., & Wetterholm, A. (2010). Advances in eicosanoid research, novel therapeutic implications. Biochemical and Biophysical Research Communications, 396(1), 135–139.PubMedGoogle Scholar
  117. 117.
    Radmark, O., & Samuelsson, B. (2010). Microsomal prostaglandin E synthase-1 and 5-lipoxygenase: potential drug targets in cancer. Journal of Internal Medicine, 268(1), 5–14.PubMedGoogle Scholar
  118. 118.
    Tanioka, T., Nakatani, Y., Semmyo, N., Murakami, M., & Kudo, I. (2000). Molecular identification of cytosolic prostaglandin E2 synthase that is functionally coupled with cyclooxygenase-1 in immediate prostaglandin E2 biosynthesis. Journal of Biological Chemistry, 275(42), 32775–32782.PubMedGoogle Scholar
  119. 119.
    Park, J. Y., Pillinger, M. H., & Abramson, S. B. (2006). Prostaglandin E2 synthesis and secretion: the role of PGE2 synthases. Clinical Immunology, 119(3), 229–240.PubMedGoogle Scholar
  120. 120.
    Lovgren, A. K., Kovarova, M., & Koller, B. H. (2007). cPGES/p23 is required for glucocorticoid receptor function and embryonic growth but not prostaglandin E2 synthesis. Molecular and Cellular Biology, 27(12), 4416–4430.PubMedGoogle Scholar
  121. 121.
    Hanaka, H., Pawelzik, S. C., Johnsen, J. I., et al. (2009). Microsomal prostaglandin E synthase 1 determines tumor growth in vivo of prostate and lung cancer cells. Proceedings of the National Academy of Sciences of the United States of America, 106(44), 18757–18762.PubMedGoogle Scholar
  122. 122.
    Amirian, E. S., Ittmann, M. M., & Scheurer, M. E. (2011). Associations between arachidonic acid metabolism gene polymorphisms and prostate cancer risk. Prostate, 71(13), 1382–1389.PubMedGoogle Scholar
  123. 123.
    Cathcart, M. C., Reynolds, J. V., O’Byrne, K. J., & Pidgeon, G. P. (2010). The role of prostacyclin synthase and thromboxane synthase signaling in the development and progression of cancer. Biochimica et Biophysica Acta, 1805(2), 153–166.PubMedGoogle Scholar
  124. 124.
    Frigola, J., Munoz, M., Clark, S. J., Moreno, V., Capella, G., & Peinado, M. A. (2005). Hypermethylation of the prostacyclin synthase (PTGIS) promoter is a frequent event in colorectal cancer and associated with aneuploidy. Oncogene, 24(49), 7320–7326.PubMedGoogle Scholar
  125. 125.
    Poole, E. M., Bigler, J., Whitton, J., Sibert, J. G., Potter, J. D., & Ulrich, C. M. (2006). Prostacyclin synthase and arachidonate 5-lipoxygenase polymorphisms and risk of colorectal polyps. Cancer Epidemiology, Biomarkers & Prevention, 15(3), 502–508.Google Scholar
  126. 126.
    Ermert, L., Dierkes, C., & Ermert, M. (2003). Immunohistochemical expression of cyclooxygenase isoenzymes and downstream enzymes in human lung tumors. Clinical Cancer Research, 9(5), 1604–1610.PubMedGoogle Scholar
  127. 127.
    Nana-Sinkam, P., Golpon, H., Keith, R. L., et al. (2004). Prostacyclin in human non-small cell lung cancers. Chest, 125(5 Suppl), 141S.PubMedGoogle Scholar
  128. 128.
    Niknami, M., Vignarajan, S., Yao, M., et al. (2010). Decrease in expression or activity of cytosolic phospholipase A2alpha increases cyclooxygenase-1 action: a cross-talk between key enzymes in arachidonic acid pathway in prostate cancer cells. Biochimica et Biophysica Acta, 1801(7), 731–737.PubMedGoogle Scholar
  129. 129.
    Nie, D., Che, M., Zacharek, A., et al. (2004). Differential expression of thromboxane synthase in prostate carcinoma: role in tumor cell motility. American Journal of Pathology, 164(2), 429–439.PubMedGoogle Scholar
  130. 130.
    Narumiya, S., Sugimoto, Y., & Ushikubi, F. (1999). Prostanoid receptors: structures, properties, and functions. Physiological Reviews, 79(4), 1193–1226.PubMedGoogle Scholar
  131. 131.
    Chen, Y., & Hughes-Fulford, M. (2000). Prostaglandin E2 and the protein kinase A pathway mediate arachidonic acid induction of c-fos in human prostate cancer cells. British Journal of Cancer, 82(12), 2000–2006.PubMedGoogle Scholar
  132. 132.
    Wang, X., & Klein, R. D. (2007). Prostaglandin E2 induces vascular endothelial growth factor secretion in prostate cancer cells through EP2 receptor-mediated cAMP pathway. Molecular Carcinogenesis, 46(11), 912–923.PubMedGoogle Scholar
  133. 133.
    Dassesse, T., de Leval, X., de Leval, L., Pirotte, B., Castronovo, V., & Waltregny, D. (2006). Activation of the thromboxane A2 pathway in human prostate cancer correlates with tumor Gleason score and pathologic stage. Eur Urol, 50(5), 1021–1031. discussion 31.PubMedGoogle Scholar
  134. 134.
    Nie, D., Guo, Y., Yang, D., et al. (2008). Thromboxane A2 receptors in prostate carcinoma: expression and its role in regulating cell motility via small GTPase rho. Cancer Research, 68(1), 115–121.PubMedGoogle Scholar
  135. 135.
    Mahmud, S., Franco, E., & Aprikian, A. (2004). Prostate cancer and use of nonsteroidal anti-inflammatory drugs: systematic review and meta-analysis. British Journal of Cancer, 90(1), 93–99.PubMedGoogle Scholar
  136. 136.
    Platz, E. A., Rohrmann, S., Pearson, J. D., et al. (2005). Nonsteroidal anti-inflammatory drugs and risk of prostate cancer in the Baltimore Longitudinal Study of Aging. Cancer Epidemiology, Biomarkers & Prevention, 14(2), 390–396.Google Scholar
  137. 137.
    Chan, J. M., Feraco, A., Shuman, M., & Hernandez-Diaz, S. (2006). The epidemiology of prostate cancer—with a focus on nonsteroidal anti-inflammatory drugs. Hematology/Oncology Clinics of North America, 20(4), 797–809.PubMedGoogle Scholar
  138. 138.
    Salinas, C. A., Kwon, E. M., FitzGerald, L. M., et al. (2010). Use of aspirin and other nonsteroidal antiinflammatory medications in relation to prostate cancer risk. American Journal of Epidemiology, 172(5), 578–590.PubMedGoogle Scholar
  139. 139.
    Wang, D., & Dubois, R. N. (2010). The role of COX-2 in intestinal inflammation and colorectal cancer. Oncogene, 29(6), 781–788.PubMedGoogle Scholar
  140. 140.
    Chapkin, R. S., Seo, J., McMurray, D. N., & Lupton, J. R. (2008). Mechanisms by which docosahexaenoic acid and related fatty acids reduce colon cancer risk and inflammatory disorders of the intestine. Chemistry and Physics of Lipids, 153(1), 14–23.PubMedGoogle Scholar
  141. 141.
    Wall, R., Ross, R. P., Fitzgerald, G. F., & Stanton, C. (2010). Fatty acids from fish: the anti-inflammatory potential of long-chain omega-3 fatty acids. Nutrition Reviews, 68(5), 280–289.PubMedGoogle Scholar
  142. 142.
    Wang, D., & DuBois, R. N. (2008). Pro-inflammatory prostaglandins and progression of colorectal cancer. Cancer Letters, 267(2), 197–203.PubMedGoogle Scholar
  143. 143.
    Wymann, M. P., & Schneiter, R. (2008). Lipid signalling in disease. Nature Reviews Molecular Cell Biology, 9(2), 162–176.PubMedGoogle Scholar
  144. 144.
    Folkman, J., Cole, P., & Zimmerman, S. (1966). Tumor behavior in isolated perfused organs: in vitro growth and metastases of biopsy material in rabbit thyroid and canine intestinal segment. Annals of Surgery, 164(3), 491–502.PubMedGoogle Scholar
  145. 145.
    Gimbrone, M. A., Jr., Leapman, S. B., Cotran, R. S., & Folkman, J. (1972). Tumor dormancy in vivo by prevention of neovascularization. The Journal of Experimental Medicine, 136(2), 261–276.PubMedGoogle Scholar
  146. 146.
    Borre, M., Offersen, B. V., Nerstrom, B., & Overgaard, J. (1998). Microvessel density predicts survival in prostate cancer patients subjected to watchful waiting. British Journal of Cancer, 78(7), 940–944.PubMedGoogle Scholar
  147. 147.
    Bono, A. V., Celato, N., Cova, V., Salvadore, M., Chinetti, S., & Novario, R. (2002). Microvessel density in prostate carcinoma. Prostate Cancer and Prostatic Diseases, 5(2), 123–127.PubMedGoogle Scholar
  148. 148.
    Ferrara, N. (2004). Vascular endothelial growth factor: basic science and clinical progress. Endocrine Reviews, 25(4), 581–611.PubMedGoogle Scholar
  149. 149.
    Tsuzuki, T., Shibata, A., Kawakami, Y., Nakagawa, K., & Miyazawa, T. (2007). Conjugated eicosapentaenoic acid inhibits vascular endothelial growth factor-induced angiogenesis by suppressing the migration of human umbilical vein endothelial cells. Journal of Nutrition, 137(3), 641–646.PubMedGoogle Scholar
  150. 150.
    Tsuji, M., Murota, S. I., & Morita, I. (2003). Docosapentaenoic acid (22:5, n-3) suppressed tube-forming activity in endothelial cells induced by vascular endothelial growth factor. Prostaglandins, Leukotrienes, and Essential Fatty Acids, 68(5), 337–342.PubMedGoogle Scholar
  151. 151.
    Yang, S. P., Morita, I., & Murota, S. I. (1998). Eicosapentaenoic acid attenuates vascular endothelial growth factor-induced proliferation via inhibiting Flk-1 receptor expression in bovine carotid artery endothelial cells. Journal of Cellular Physiology, 176(2), 342–349.PubMedGoogle Scholar
  152. 152.
    Calviello, G., Di Nicuolo, F., Gragnoli, S., et al. (2004). n-3 PUFAs reduce VEGF expression in human colon cancer cells modulating the COX-2/PGE2 induced ERK-1 and -2 and HIF-1alpha induction pathway. Carcinogenesis, 25(12), 2303–2310.PubMedGoogle Scholar
  153. 153.
    Connor, K. M., SanGiovanni, J. P., Lofqvist, C., et al. (2007). Increased dietary intake of omega-3-polyunsaturated fatty acids reduces pathological retinal angiogenesis. Nature Medicine, 13(7), 868–873.PubMedGoogle Scholar
  154. 154.
    Stahl, A., Sapieha, P., Connor, K. M., et al. (2010). Short communication: PPAR gamma mediates a direct antiangiogenic effect of omega 3-PUFAs in proliferative retinopathy. Circulation Research, 107(4), 495–500.PubMedGoogle Scholar
  155. 155.
    Sapieha, P., Stahl, A., Chen, J., et al. (2011). 5-Lipoxygenase metabolite 4-HDHA is a mediator of the antiangiogenic effect of {omega}-3 polyunsaturated fatty acids. Science Translational Medicine, 3(69), 69ra12.PubMedGoogle Scholar
  156. 156.
    Rose, D. P., & Connolly, J. M. (1999). Antiangiogenicity of docosahexaenoic acid and its role in the suppression of breast cancer cell growth in nude mice. International Journal of Oncology, 15(5), 1011–1015.PubMedGoogle Scholar
  157. 157.
    Ambring, A., Johansson, M., Axelsen, M., Gan, L., Strandvik, B., & Friberg, P. (2006). Mediterranean-inspired diet lowers the ratio of serum phospholipid n-6 to n-3 fatty acids, the number of leukocytes and platelets, and vascular endothelial growth factor in healthy subjects. American Journal of Clinical Nutrition, 83(3), 575–581.PubMedGoogle Scholar
  158. 158.
    Fox, P. L., & DiCorleto, P. E. (1988). Fish oils inhibit endothelial cell production of platelet-derived growth factor-like protein. Science, 241(4864), 453–456.PubMedGoogle Scholar
  159. 159.
    Kaminski, W. E., Jendraschak, E., Kiefl, R., & von Schacky, C. (1993). Dietary omega-3 fatty acids lower levels of platelet-derived growth factor mRNA in human mononuclear cells. Blood, 81(7), 1871–1879.PubMedGoogle Scholar
  160. 160.
    Powers, C. J., McLeskey, S. W., & Wellstein, A. (2000). Fibroblast growth factors, their receptors and signaling. Endocrine-Related Cancer, 7(3), 165–197.PubMedGoogle Scholar
  161. 161.
    Ornitz, D. M., & Itoh, N. (2001). Fibroblast growth factors. Genome Biology, 2(3), REVIEWS3005.PubMedGoogle Scholar
  162. 162.
    Kwabi-Addo, B., Ozen, M., & Ittmann, M. (2004). The role of fibroblast growth factors and their receptors in prostate cancer. Endocrine-Related Cancer, 11(4), 709–724.PubMedGoogle Scholar
  163. 163.
    Li, Z. G., Mathew, P., Yang, J., et al. (2008). Androgen receptor-negative human prostate cancer cells induce osteogenesis in mice through FGF9-mediated mechanisms. The Journal of Clinical Investigation, 118(8), 2697–2710.PubMedGoogle Scholar
  164. 164.
    Heer, R., Douglas, D., Mathers, M. E., Robson, C. N., & Leung, H. Y. (2004). Fibroblast growth factor 17 is over-expressed in human prostate cancer. The Journal of Pathology, 204(5), 578–586.PubMedGoogle Scholar
  165. 165.
    Folkman, J., & Shing, Y. (1992). Angiogenesis. Journal of Biological Chemistry, 267(16), 10931–10934.PubMedGoogle Scholar
  166. 166.
    Dorkin, T. J., Robinson, M. C., Marsh, C., Neal, D. E., & Leung, H. Y. (1999). aFGF immunoreactivity in prostate cancer and its co-localization with bFGF and FGF8. The Journal of Pathology, 189(4), 564–569.PubMedGoogle Scholar
  167. 167.
    Polnaszek, N., Kwabi-Addo, B., Peterson, L. E., et al. (2003). Fibroblast growth factor 2 promotes tumor progression in an autochthonous mouse model of prostate cancer. Cancer Research, 63(18), 5754–5760.PubMedGoogle Scholar
  168. 168.
    Gnanapragasam, V. J., Robinson, M. C., Marsh, C., Robson, C. N., Hamdy, F. C., & Leung, H. Y. (2003). FGF8 isoform b expression in human prostate cancer. British Journal of Cancer, 88(9), 1432–1438.PubMedGoogle Scholar
  169. 169.
    Valta, M. P., Tuomela, J., Vuorikoski, H., et al. (2009). FGF-8b induces growth and rich vascularization in an orthotopic PC-3 model of prostate cancer. Journal of Cellular Biochemistry, 107(4), 769–784.PubMedGoogle Scholar
  170. 170.
    Elo, T. D., Valve, E. M., Seppanen, J. A., et al. (2010). Stromal activation associated with development of prostate cancer in prostate-targeted fibroblast growth factor 8b transgenic mice. Neoplasia, 12(11), 915–927.PubMedGoogle Scholar
  171. 171.
    Kasayama, S., Koga, M., Kouhara, H., et al. (1994). Unsaturated fatty acids are required for continuous proliferation of transformed androgen-dependent cells by fibroblast growth factor family proteins. Cancer Research, 54(24), 6441–6445.PubMedGoogle Scholar
  172. 172.
    Iwasaki, A., & Medzhitov, R. (2004). Toll-like receptor control of the adaptive immune responses. Nature Immunology, 5(10), 987–995.PubMedGoogle Scholar
  173. 173.
    Huang, B., Zhao, J., Li, H., et al. (2005). Toll-like receptors on tumor cells facilitate evasion of immune surveillance. Cancer Research, 65(12), 5009–5014.PubMedGoogle Scholar
  174. 174.
    Kelly, M. G., Alvero, A. B., Chen, R., et al. (2006). TLR-4 signaling promotes tumor growth and paclitaxel chemoresistance in ovarian cancer. Cancer Research, 66(7), 3859–3868.PubMedGoogle Scholar
  175. 175.
    Rakoff-Nahoum, S., & Medzhitov, R. (2009). Toll-like receptors and cancer. Nature Reviews Cancer, 9(1), 57–63.PubMedGoogle Scholar
  176. 176.
    Zheng, S. L., Augustsson-Balter, K., Chang, B., et al. (2004). Sequence variants of toll-like receptor 4 are associated with prostate cancer risk: results from the Cancer Prostate in Sweden Study. Cancer Research, 64(8), 2918–2922.PubMedGoogle Scholar
  177. 177.
    Sun, J., Wiklund, F., Zheng, S. L., et al. (2005). Sequence variants in toll-like receptor gene cluster (TLR6-TLR1-TLR10) and prostate cancer risk. Journal of the National Cancer Institute, 97(7), 525–532.PubMedGoogle Scholar
  178. 178.
    Lee, J. Y., Plakidas, A., Lee, W. H., et al. (2003). Differential modulation of toll-like receptors by fatty acids: preferential inhibition by n-3 polyunsaturated fatty acids. Journal of Lipid Research, 44(3), 479–486.PubMedGoogle Scholar
  179. 179.
    Lee, J. Y., Zhao, L., Youn, H. S., et al. (2004). Saturated fatty acid activates but polyunsaturated fatty acid inhibits toll-like receptor 2 dimerized with toll-like receptor 6 or 1. Journal of Biological Chemistry, 279(17), 16971–16979.PubMedGoogle Scholar
  180. 180.
    Paone, A., Galli, R., Gabellini, C., et al. (2010). Toll-like receptor 3 regulates angiogenesis and apoptosis in prostate cancer cell lines through hypoxia-inducible factor 1 alpha. Neoplasia, 12(7), 539–549.PubMedGoogle Scholar
  181. 181.
    Rapraeger, A., Jalkanen, M., Endo, E., Koda, J., & Bernfield, M. (1985). The cell surface proteoglycan from mouse mammary epithelial cells bears chondroitin sulfate and heparan sulfate glycosaminoglycans. Journal of Biological Chemistry, 260(20), 11046–11052.PubMedGoogle Scholar
  182. 182.
    Manon-Jensen, T., Itoh, Y., & Couchman, J. R. (2010). Proteoglycans in health and disease: the multiple roles of syndecan shedding. The FEBS Journal, 277(19), 3876–3889.PubMedGoogle Scholar
  183. 183.
    Inki, P., & Jalkanen, M. (1996). The role of syndecan-1 in malignancies. Annali Medici, 28(1), 63–67.Google Scholar
  184. 184.
    Matsumoto, A., Ono, M., Fujimoto, Y., Gallo, R. L., Bernfield, M., & Kohgo, Y. (1997). Reduced expression of syndecan-1 in human hepatocellular carcinoma with high metastatic potential. International Journal of Cancer, 74(5), 482–491.Google Scholar
  185. 185.
    Kumar-Singh, S., Jacobs, W., Dhaene, K., et al. (1998). Syndecan-1 expression in malignant mesothelioma: correlation with cell differentiation, WT1 expression, and clinical outcome. The Journal of Pathology, 186(3), 300–305.PubMedGoogle Scholar
  186. 186.
    Loussouarn, D., Campion, L., Sagan, C., et al. (2008). Prognostic impact of syndecan-1 expression in invasive ductal breast carcinomas. British Journal of Cancer, 98(12), 1993–1998.PubMedGoogle Scholar
  187. 187.
    Barbareschi, M., Maisonneuve, P., Aldovini, D., et al. (2003). High syndecan-1 expression in breast carcinoma is related to an aggressive phenotype and to poorer prognosis. Cancer, 98(3), 474–483.PubMedGoogle Scholar
  188. 188.
    Davies, E. J., Blackhall, F. H., Shanks, J. H., et al. (2004). Distribution and clinical significance of heparan sulfate proteoglycans in ovarian cancer. Clinical Cancer Research, 10(15), 5178–5186.PubMedGoogle Scholar
  189. 189.
    Choi, D. S., Kim, J. H., Ryu, H. S., et al. (2007). Syndecan-1, a key regulator of cell viability in endometrial cancer. International Journal of Cancer, 121(4), 741–750.Google Scholar
  190. 190.
    Stanley, M. J., Stanley, M. W., Sanderson, R. D., & Zera, R. (1999). Syndecan-1 expression is induced in the stroma of infiltrating breast carcinoma. American Journal of Clinical Pathology, 112(3), 377–383.PubMedGoogle Scholar
  191. 191.
    Mennerich, D., Vogel, A., Klaman, I., et al. (2004). Shift of syndecan-1 expression from epithelial to stromal cells during progression of solid tumours. European Journal of Cancer, 40(9), 1373–1382.PubMedGoogle Scholar
  192. 192.
    Wiksten, J. P., Lundin, J., Nordling, S., et al. (2001). Epithelial and stromal syndecan-1 expression as predictor of outcome in patients with gastric cancer. International Journal of Cancer, 95(1), 1–6.Google Scholar
  193. 193.
    Kiviniemi, J., Kallajoki, M., Kujala, I., et al. (2004). Altered expression of syndecan-1 in prostate cancer. APMIS, 112(2), 89–97.PubMedGoogle Scholar
  194. 194.
    Chen, D., Adenekan, B., Chen, L., et al. (2004). Syndecan-1 expression in locally invasive and metastatic prostate cancer. Urology, 63(2), 402–407.PubMedGoogle Scholar
  195. 195.
    Zellweger, T., Ninck, C., Mirlacher, M., et al. (2003). Tissue microarray analysis reveals prognostic significance of syndecan-1 expression in prostate cancer. Prostate, 55(1), 20–29.PubMedGoogle Scholar
  196. 196.
    Hu, Y., Sun, H., Owens, R. T., et al. (2010). Syndecan-1-dependent suppression of PDK1/Akt/bad signaling by docosahexaenoic acid induces apoptosis in prostate cancer. Neoplasia, 12(10), 826–836.PubMedGoogle Scholar
  197. 197.
    Edwards, I. J., Sun, H., Hu, Y., et al. (2008). In vivo and in vitro regulation of syndecan 1 in prostate cells by N-3 polyunsaturated fatty acids. Journal of Biological Chemistry, 283(26), 18441–18449.PubMedGoogle Scholar
  198. 198.
    Edwards, I. J., Berquin, I. M., Sun, H., et al. (2004). Differential effects of delivery of omega-3 fatty acids to human cancer cells by low-density lipoproteins versus albumin. Clinical Cancer Research, 10(24), 8275–8283.PubMedGoogle Scholar
  199. 199.
    Sun, H., Berquin, I. M., & Edwards, I. J. (2005). Omega-3 polyunsaturated fatty acids regulate syndecan-1 expression in human breast cancer cells. Cancer Research, 65(10), 4442–4447.PubMedGoogle Scholar
  200. 200.
    Park, P. W., Pier, G. B., Hinkes, M. T., & Bernfield, M. (2001). Exploitation of syndecan-1 shedding by Pseudomonas aeruginosa enhances virulence. Nature, 411(6833), 98–102.PubMedGoogle Scholar
  201. 201.
    Li, Q., Park, P. W., Wilson, C. L., & Parks, W. C. (2002). Matrilysin shedding of syndecan-1 regulates chemokine mobilization and transepithelial efflux of neutrophils in acute lung injury. Cell, 111(5), 635–646.PubMedGoogle Scholar
  202. 202.
    Xu, J., Park, P. W., Kheradmand, F., & Corry, D. B. (2005). Endogenous attenuation of allergic lung inflammation by syndecan-1. Journal of Immunology, 174(9), 5758–5765.Google Scholar
  203. 203.
    Gotte, M., Joussen, A. M., Klein, C., et al. (2002). Role of syndecan-1 in leukocyte-endothelial interactions in the ocular vasculature. Investigative Ophthalmology & Visual Science, 43(4), 1135–1141.Google Scholar
  204. 204.
    Gotte, M., Bernfield, M., & Joussen, A. M. (2005). Increased leukocyte-endothelial interactions in syndecan-1-deficient mice involve heparan sulfate-dependent and -independent steps. Current Eye Research, 30(6), 417–422.PubMedGoogle Scholar
  205. 205.
    Gardiner, T. A., Gibson, D. S., de Gooyer, T. E., de la Cruz, V. F., McDonald, D. M., & Stitt, A. W. (2005). Inhibition of tumor necrosis factor-alpha improves physiological angiogenesis and reduces pathological neovascularization in ischemic retinopathy. American Journal of Pathology, 166(2), 637–644.PubMedGoogle Scholar
  206. 206.
    Kainulainen, V., Nelimarkka, L., Jarvelainen, H., Laato, M., Jalkanen, M., & Elenius, K. (1996). Suppression of syndecan-1 expression in endothelial cells by tumor necrosis factor-alpha. Journal of Biological Chemistry, 271(31), 18759–18766.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Isabelle M. Berquin
    • 1
    • 3
  • Iris J. Edwards
    • 2
    • 3
  • Steven J. Kridel
    • 1
    • 3
  • Yong Q. Chen
    • 1
    • 3
  1. 1.Department of Cancer BiologyWake Forest School of MedicineWinston-SalemUSA
  2. 2.Department of PathologyWake Forest School of MedicineWinston-SalemUSA
  3. 3.Comprehensive Cancer CenterWake Forest School of MedicineWinston-SalemUSA

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