Potential Mechanisms Linking Oxidized LDL to Susceptibility to Cancer

Chapter

Abstract

Last decades have witnessed an explosive growth of obesity in developed countries. This condition is associated with not only increased risk for atherosclerosis and resultant cardiovascular pathologies but also confers significant increase in probability for the development of various forms of cancer. Experimental and epidemiological evidence accumulated in respective fields highlights multiple overlaps in pathobiology of atherosclerosis and cancer including signaling pathways, inflammation, cytokine involvement, proliferation, and angiogenesis. Recent discovery of additional layer of regulation of gene expression based on miRNAs also revealed multiple similarities in miRNA profiles. This suggests that atherogenesis and obesity-­mediated increase in susceptibility to cancers may have common etiological roots. Recent advances in cardiovascular research identified oxidatively modified LDL (and not LDL itself) as a primary factor responsible for initiation and progression of atherogenesis, and the analysis of potential involvement of ox-LDL in carcinogenesis is the focus of the present review.

Keywords

Ox-LDL Cancer Inflammation Angiogenesis miRNAs 

References

  1. 1.
    Renehan AG, Tyson M, Egger M et al (2008) Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet 371:569–578PubMedGoogle Scholar
  2. 2.
    Renehan AG, Soerjomataram I, Leitzmann MF (2010) Interpreting the epidemiological evidence linking obesity and cancer: a framework for population-attributable risk estimations in Europe. Eur J Cancer 46:2581–2592PubMedGoogle Scholar
  3. 3.
    Calle EE, Rodriguez C, Walker-Thurmond K et al (2003) Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med 348:1625–1638PubMedGoogle Scholar
  4. 4.
    Grek CL, Tew KD (2010) Redox metabolism and malignancy. Curr Opin Pharmacol 4:362–368Google Scholar
  5. 5.
    Trinchieri G (2012) Cancer and inflammation: an old intuition with rapidly evolving new concepts. Annu Rev Immunol 30:677–706PubMedGoogle Scholar
  6. 6.
    Kelesidis I, Kelesidis T, Mantzoros CS (2006) Adiponectin and cancer: a systematic review. Br J Cancer 94:1221–1225PubMedGoogle Scholar
  7. 7.
    Braun S, Bitton-Worms K, LeRoith D (2011) The link between the metabolic syndrome and cancer. Int J Biol Sci 7:1003–1015PubMedGoogle Scholar
  8. 8.
    Wang D, Dubois RN (2012) The role of the PGE2-aromatase pathway in obesity-associated breast inflammation. Cancer Discov 2:308–310PubMedGoogle Scholar
  9. 9.
    Brown MS, Kovanen PT, Goldstein JL (1981) Regulation of plasma cholesterol by lipoprotein receptors. Science 212:628–635PubMedGoogle Scholar
  10. 10.
    Vykhovanets EV, Shankar E, Vykhovanets OV et al (2011) High-fat diet increases NF-κB signaling in the prostate of reporter mice. Prostate 71:147–156PubMedGoogle Scholar
  11. 11.
    Bełtowski J, Wójcicka G, Górny D et al (2000) The effect of dietary-induced obesity on lipid peroxidation, antioxidant enzymes and total plasma antioxidant capacity. J Physiol Pharmacol 51:883–896PubMedGoogle Scholar
  12. 12.
    Brinkley TE, Kume N, Mitsuoka H et al (2008) Elevated soluble lectin-like oxidized LDL receptor-1 [sLOX-1] levels in obese postmenopausal women. Obesity (Silver Spring) 16:1454–1456Google Scholar
  13. 13.
    Holvoet P (2008) Relations between metabolic syndrome, oxidative stress and inflammation and cardiovascular disease. Verh K Acad Geneeskd Belg 70:193–219PubMedGoogle Scholar
  14. 14.
    Holvoet P, Lee DH, Steffes M et al (2008) Association between circulating oxidized low-­density lipoprotein and incidence of the metabolic syndrome. JAMA 299:2287–2293PubMedGoogle Scholar
  15. 15.
    Holvoet P, Kritchevsky SB, Tracy RP et al (2004) The metabolic syndrome, circulating oxidized LDL and risk of myocardial infarction in well-functioning elderly people in the health, aging, and body composition cohort. Diabetes 53:1068–1073PubMedGoogle Scholar
  16. 16.
    Meisinger C, Baumert J, Khuseyinova N et al (2005) Plasma oxidized low-density lipoprotein, a strong predictor for acute coronary heart disease events in apparently healthy, middleaged men from the general population. Circulation 112:651–657PubMedGoogle Scholar
  17. 17.
    Steinberg D, Parthasarathy S, Carew TE et al (1989) Beyond cholesterol: modifications of low density lipoprotein that increase its atherogenicity. N Engl J Med 320:915–924PubMedGoogle Scholar
  18. 18.
    Haberland ME, Fogelman AM, Edwards PA (1982) Specificity of receptor-mediated recognition of malondialdehyde-modified low density lipoproteins. Proc Natl Acad Sci U S A 79:1712–1716PubMedGoogle Scholar
  19. 19.
    Parthasarathy S, Fong LG, Otero D et al (1987) Recognition of solubilized apoproteins from delipidated, oxidized low density lipoprotein [LDL] by the acetyl-LDL receptor. Proc Natl Acad Sci U S A 84:537–540PubMedGoogle Scholar
  20. 20.
    Li D, Mehta JL (2000) Upregulation of endothelial receptor for oxidized LDL [LOX-1] by oxidized LDL and implications in apoptosis of human coronary artery endothelial cells. Arterioscler Thromb Vasc Biol 20:1116–1122PubMedGoogle Scholar
  21. 21.
    Nicholson AC, Han J, Febbraio M et al (2001) Role of CD36, the macrophage class B scavenger receptor, in atherosclerosis. Ann N Y Acad Sci 947:224–228PubMedGoogle Scholar
  22. 22.
    Marnett LJ (1999) Chemistry and biology of DNA damage by malondialdehyde. IARC Sci Publ 150:17–27PubMedGoogle Scholar
  23. 23.
    Esterbauer H, Schaur RJ, Zollner H (1991) Chemistry and biochemistry of 4-­hydroxynonenal, malonaldehyde and related aldehydes. Free Radic Biol Med 11(1):81–128PubMedGoogle Scholar
  24. 24.
    Feng Z, Hu W, Tang MS (2004) Trans-4-hydroxy-2-nonenal inhibits nucleotide excision repair in human cells: a possible mechanism for lipid peroxidation-induced carcinogenesis. Proc Natl Acad Sci U S A 101:8598–8602PubMedGoogle Scholar
  25. 25.
    Chen KH, Srivastava DK, Singhal RK et al (2000) Modulation of base excision repair by low density lipoprotein, oxidized low density lipoprotein and antioxidants in mouse monocytes. Carcinogenesis 21:1017–1022PubMedGoogle Scholar
  26. 26.
    Thum T, Borlak J (2008) LOX-1 receptor blockade abrogates oxLDL-induced oxidative DNA damage and prevents activation of the transcriptional repressor Oct-1 in human coronary arterial endothelium. Biol Chem 283:19456–19464Google Scholar
  27. 27.
    Inoue T, Inoue K, Maeda H et al (2001) Immunological response to oxidized LDL occurs in association with oxidative DNA damage independently of serum LDL concentrations in dyslipidemic patients. Clin Chim Acta 305:115–121PubMedGoogle Scholar
  28. 28.
    Rueckschloss U, Galle J, Holtz J et al (2001) Induction of NAD[P]H oxidase by oxidized low-density lipoprotein in human endothelial cells: antioxidative potential of hydroxymethylglutaryl coenzyme A reductase inhibitor therapy. Circulation 104:1767–1772PubMedGoogle Scholar
  29. 29.
    Bae YS, Lee JH, Choi SH et al (2009) Macrophages generate reactive oxygen species in response to minimally oxidized low-density lipoprotein: toll-like receptor 4- and spleen tyrosine kinase-dependent activation of NADPH oxidase 2. Circ Res 104:210–218PubMedGoogle Scholar
  30. 30.
    Zhao R, Moghadasian MH, Shen GX (2011) Involvement of NADPH oxidase in up-­regulation of plasminogen activator inhibitor-1 and heat shock factor-1 in mouse embryo fibroblasts induced by oxidized LDL and in apolipoprotein E-deficient mice. Free Radic Res 45:1013–1023PubMedGoogle Scholar
  31. 31.
    Landar A, Zmijewski JW, Dickinson DA et al (2006) Interaction of electrophilic lipid oxidation products with mitochondria in endothelial cells and formation of reactive oxygen species. Am J Physiol Heart Circ Physiol 290:H1777–H1787PubMedGoogle Scholar
  32. 32.
    Zmijewski JW, Moellering DR, Le Goffe C et al (2005) Oxidized LDL induces mitochondrially associated reactive oxygen/nitrogen species formation in endothelial cells. Am J Physiol Heart Circ Physiol 289:H852–H861PubMedGoogle Scholar
  33. 33.
    Takabe W, Li R, Ai L et al (2010) Oxidized low-density lipoprotein-activated c-Jun NH2-­terminal kinase regulates manganese superoxide dismutase ubiquitination: implication for mitochondrial redox status and apoptosis. Arterioscler Thromb Vasc Biol 30:436–441PubMedGoogle Scholar
  34. 34.
    Ceaser EK, Ramachandran A, Levonen AL et al (2003) Oxidized low-density lipoprotein and 15-deoxy-Delta 12,14-PGJ2 increase mitochondrial complex I activity in endothelial cells. Am J Physiol Heart Circ Physiol 285:H2298–H2308PubMedGoogle Scholar
  35. 35.
    Jiang F, Lim HK, Morris MJ et al (2011) Systemic upregulation of NADPH oxidase in diet-­induced obesity in rats. Redox Rep 16:223–229PubMedGoogle Scholar
  36. 36.
    Kamata T (2009) Roles of Nox1 and other Nox isoforms in cancer development. Cancer Sci 100:1382–1388PubMedGoogle Scholar
  37. 37.
    Ranjan P, Anathy V, Burch PM et al (2006) Redox-dependent expression of cyclin D1 and cell proliferation by Nox1 in mouse lung epithelial cells. Antioxid Redox Signal 8:1447–1459PubMedGoogle Scholar
  38. 38.
    Mitsushita J, Lambeth JD, Kamata T (2004) The superoxide-generating oxidase Nox1 is functionally required for Ras oncogene transformation. Cancer Res 64:3580–3585PubMedGoogle Scholar
  39. 39.
    Irani K, Xia Y, Zweier JL et al (1997) Mitogenic signaling mediated by oxidants in Ras-­transformed fibroblasts. Science 275:1649–1652PubMedGoogle Scholar
  40. 40.
    Suh YA, Arnold RS, Lassegue B et al (1999) Cell transformation by the superoxide-­generating oxidase Mox1. Nature 401:79–82PubMedGoogle Scholar
  41. 41.
    Puca R, Nardinocchi L, Starace G et al (2010) Nox1 is involved in p53 deacetylation and suppression of its transcriptional activity and apoptosis. Free Radic Biol Med 48:1338–1346PubMedGoogle Scholar
  42. 42.
    Graham KA, Kulawiec M, Owens KM et al (2010) NADPH oxidase 4 is an oncoprotein loc.lized to mitochondria. Cancer Biol Ther 10:223–231PubMedGoogle Scholar
  43. 43.
    Roy Chowdhury SK, Sangle GV, Xie X et al (2010) Effects of extensively oxidized low-­density lipoprotein on mitochondrial function and reactive oxygen species in porcine aortic endothelial cells. Am J Physiol Endocrinol Metab 298:E89–E98PubMedGoogle Scholar
  44. 44.
    Nowsheen S, Aziz K, Kryston TB et al (2012) The interplay between inflammation and oxidative stress in carcinogenesis. Curr Mol Med 12:672–680PubMedGoogle Scholar
  45. 45.
    Reedy J (1975) Galen on cancer and related diseases. Clio Med 10:227–238PubMedGoogle Scholar
  46. 46.
    Balkwill F, Mantovani A (2001) Inflammation and cancer: back to Virchow? Lancet 357:539–545PubMedGoogle Scholar
  47. 47.
    Norris AL, Steinberger J, Steffen LM et al (2011) Circulating oxidized LDL and inflammation in extreme pediatric obesity. Obesity (Silver Spring) 19:1415–1419Google Scholar
  48. 48.
    Hulthe J, Fagerberg B (2002) Circulating oxidized LDL is associated with subclinical atherosclerosis development and inflammatory cytokines [AIR Study] arteriosclerosis. Arterioscler Thromb Vasc Biol 22:1162–1167PubMedGoogle Scholar
  49. 49.
    Ishikawa M, Ito H, Akiyoshi M et al (2012) Lectin-like oxidized low-density lipoprotein receptor 1 signal is a potent biomarker and therapeutic target for human rheumatoid arthritis. Arthritis Rheum 64:1024–1034PubMedGoogle Scholar
  50. 50.
    Cominacini L, Pasini AF, Garbin U et al (2000) Oxidized low density lipoprotein [ox-LDL] binding to ox-LDL receptor-1 in endothelial cells induces the activation of NF-κB through an increased production of intracellular reactive oxygen species. J Biol Chem 275:12633–12638PubMedGoogle Scholar
  51. 51.
    Matsunaga T, Hokari S, Koyama I et al (2003) NF-kappa B activation in endothelial cells treated with oxidized high-density lipoprotein. Biochem Biophys Res Commun 303:313–319PubMedGoogle Scholar
  52. 52.
  53. 53.
    Rayet B, Gélinas C (1999) Aberrant rel/nfkb genes and activity in human cancer. Oncogene 18:6938–6947PubMedGoogle Scholar
  54. 54.
    Sun XF, Zhang H (2007) NFKB and NFKBI polymorphisms in relation to susceptibility of tumour and other diseases. Histol Histopathol 22:1387–1398PubMedGoogle Scholar
  55. 55.
    Hirsch HA, Iliopoulos D, Joshi A et al (2010) A transcriptional signature and common gene networks link cancer with lipid metabolism and diverse human diseases. Cancer Cell 17:348–356PubMedGoogle Scholar
  56. 56.
    Kang BY, Hu C, Prayaga S et al (2009) LOX-1 dependent overexpression of immunoglobulins in cardiomyocytes in response to angiotensin II. Biochem Biophys Res Commun 379:395–399PubMedGoogle Scholar
  57. 57.
    Khaidakov M, Mitra S, Kadlubar S et al (2011) Oxidized LDL receptor 1 [LOX-1] as a possible link between obesity and cancer. PLoS One 6(5):e20277PubMedGoogle Scholar
  58. 58.
    Maziere C, Auclair M, Djavaheri-Mergny M et al (1996) Oxidized low density lipoprotein induces activation of the transcription factor NF kappa B in fibroblasts, endothelial and smooth muscle cells. Biochem Mol Biol Int 39:1201–1207PubMedGoogle Scholar
  59. 59.
    Calara F, Dimayuga P, Niemann A et al (1998) An animal model to study local oxidation of LDL and its biological effects in the arterial wall. Arterioscler Thromb Vasc Biol 18:884–893PubMedGoogle Scholar
  60. 60.
    Nishimura S, Akagi M, Yoshida K et al (2004) Oxidized low-density lipoprotein [ox-LDL] binding to lectin-like ox-LDL receptor-1 [LOX-1] in cultured bovine articular chondrocytes increases production of intracellular reactive oxygen species [ROS] resulting in the activation of NF-kappaB. Osteoarthritis Cartilage 12:568–576PubMedGoogle Scholar
  61. 61.
    Fajardo LF, Kwan HH, Kowalski J et al (1992) Dual role of tumor necrosis factor-alpha in angiogenesis. Am J Pathol 140:539–544PubMedGoogle Scholar
  62. 62.
    Beg AA, Finco TS, Nantermet PV et al (1993) Tumor necrosis factor and interleukin-1 lead to phosphorylation and loss of I kappa B alpha: a mechanism for NF-kappa B activation. Mol Cell Biol 13:3301–3310PubMedGoogle Scholar
  63. 63.
    Moore RJ, Owens DM, Stamp G et al (1999) Mice deficient in tumor necrosis factor-alpha are resistant to skin carcinogenesis. Nat Med 5:828–831PubMedGoogle Scholar
  64. 64.
    Schmid MC, Avraamides CJ, Foubert P et al (2011) Combined blockade of integrin-α4β1 plus cytokines SDF-1α or IL-1β potently inhibits tumor inflammation and growth. Cancer Res 71:6965–6975PubMedGoogle Scholar
  65. 65.
    Tsirakis G, Pappa CA, Kaparou M et al (2011) Assessment of proliferating cell nuclear antigen and its relationship with proinflammatory cytokines and parameters of disease activity in multiple myeloma patients. Eur J Histochem 55:e21PubMedGoogle Scholar
  66. 66.
    Heikkilä K, Ebrahim S, Lawlor DA (2008) Systematic review of the association between circulating interleukin-6 [IL-6] and cancer. Eur J Cancer 44:937–945PubMedGoogle Scholar
  67. 67.
    Kishimoto T (2005) Interleukin-6: from basic science to medicine–40 years in immunology. Annu Rev Immunol 23:1–21PubMedGoogle Scholar
  68. 68.
    Becker C, Fantini MC, Wirtz S et al (2005) IL-6 signaling promotes tumor growth in colorectal cancer. Cell Cycle 4:217–220PubMedGoogle Scholar
  69. 69.
    Yun UJ, Park SE, Jo YS et al (2012) DNA damage induces the IL-6/STAT3 signaling pathway, which has anti-senescence and growth-promoting functions in human tumors. Cancer Lett 323:155–160PubMedGoogle Scholar
  70. 70.
    Waugh DJJ, Wilson C (2008) The interleukin-8 pathway in cancer. Clin Cancer Res 14:6735–6741PubMedGoogle Scholar
  71. 71.
    Kuniyasu A, Hayashi S, Nakayama H (2002) Adipocytes recognize and degrade oxidized low density lipoprotein through CD36. Biochem Biophys Res Commun 295:319–323PubMedGoogle Scholar
  72. 72.
    Terkeltaub R, Banka CL, Solan J et al (1994) Oxidized LDL induces monocytic cell expression of interleukin-8, a chemokine with T-lymphocyte chemotactic activity. Arterioscler Thromb 14:47–53PubMedGoogle Scholar
  73. 73.
    van Tits LJ, Stienstra R, van Lent PL et al (2011) Oxidized LDL enhances pro-inflammatory responses of alternatively activated M2 macrophages: a crucial role for Krüppel-like factor 2. Atherosclerosis 214:345–349PubMedGoogle Scholar
  74. 74.
    Shao Q, Shen LH, Hu LH et al (2010) Nuclear receptor Nur77 suppresses inflammatory response dependent on COX-2 in macrophages induced by oxLDL. J Mol Cell Cardiol 49:304–311PubMedGoogle Scholar
  75. 75.
    Xie C, Ng H, Nagarajan S (2011) OxLDL or TLR2-induced cytokine response is enhanced by oxLDL-independent novel domain on mouse CD36. Immunol Lett 137:15–27PubMedGoogle Scholar
  76. 76.
    Chávez-Sánchez L, Chávez-Rueda K, Legorreta-Haquet MV et al (2010) The activation of CD14, TLR4, and TLR2 by mmLDL induces IL-1β, IL-6, and IL-10 secretion in human monocytes and macrophages. Lipids Health Dis 9:117PubMedGoogle Scholar
  77. 77.
    Li HX, Lei L, Yan FH (2010) Changes in cytokine levels during foam cells formation induced by oxidized low density lipoprotein stimulation. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 26:742–745PubMedGoogle Scholar
  78. 78.
    Uyemura K, Demer LL, Castle SC et al (1996) Cross-regulatory roles of interleukin [IL]-12 and IL-10 in atherosclerosis. J Clin Invest 97:2130–2138PubMedGoogle Scholar
  79. 79.
    Jovinge S, Ares MPS, Kallin B et al (1996) Human monocytes/macrophages release TNF-α in response to Ox-LDL. Arterioscler Thromb Vasc Biol 6:1573–1579Google Scholar
  80. 80.
    Jiang YR, Miao Y, Yang L et al (2012) Effect of chinese herbal drug-containing serum for activating-blood and dispelling-toxin on ox-LDL-induced inflammatory factors’ expression in endothelial cells. Chin J Integr Med 18:30–33PubMedGoogle Scholar
  81. 81.
    Hoffmann CJ, Hohberg M, Chlench S et al (2011) Suppression of zinc finger protein 580 by high oxLDL/LDL-ratios is followed by enhanced expression of endothelial IL-8. Atherosclerosis 216:103–108PubMedGoogle Scholar
  82. 82.
    Costa S, Zimetti F, Pedrelli M et al (2010) Manidipine reduces pro-inflammatory cytokines secretion in human endothelial cells and macrophages. Pharmacol Res 62:265–270PubMedGoogle Scholar
  83. 83.
    Mattaliano MD, Wooters J, Shih HH et al (2010) ROCK2 associates with lectin-like oxidized LDL receptor-1 and mediates oxidized LDL-induced IL-8 production. Am J Physiol Cell Physiol 298:C1180–C1187PubMedGoogle Scholar
  84. 84.
    Lappalainen J, Lindstedt KA, Oksjoki R et al (2011) OxLDL-IgG immune complexes induce expression and secretion of proatherogenic cytokines by cultured human mast cells. Atherosclerosis 214:357–363PubMedGoogle Scholar
  85. 85.
    Nagahama Y, Obama T, Usui M et al (2011) Oxidized low-density lipoprotein-induced ­periodontal inflammation is associated with the up-regulation of cyclooxygenase-2 and microsomal prostaglandin synthase 1 in human gingival epithelial cells. Biochem Biophys Res Commun 413:566–571PubMedGoogle Scholar
  86. 86.
    Suzuki K, Sakiyama Y, Usui M et al (2010) Oxidized low-density lipoprotein increases interleukin-­8 production in human gingival epithelial cell line Ca9-22. J Periodontal Res 45:488–495PubMedGoogle Scholar
  87. 87.
    Yimin, Furumaki H, Matsuoka S et al (2010) A novel murine model for non-alcoholic steatohepatitis developed by combination of a high-fat diet and oxidized low-density lipoprotein. Lab Invest 92:265–281Google Scholar
  88. 88.
    Park J, Euhus DM, Scherer PE (2011) Paracrine and endocrine effects of adipose tissue on cancer development and progression. Endocr Rev 32:550–570PubMedGoogle Scholar
  89. 89.
    Matsubara M, Maruoka S, Katayose S (2002) Inverse relationship between plasma adiponectin and leptin concentrations in normal-weight and obese women. Eur J Endocrinol 147:173–180PubMedGoogle Scholar
  90. 90.
    Wauman J, Tavernier J (2011) Leptin receptor signaling: pathways to leptin resistance. Front Biosci 17:2771–2793Google Scholar
  91. 91.
    Ukropec J, Seböková E, Klimes I (2001) Nutrient sensing, leptin and insulin action. Arch Physiol Biochem 109:38–51PubMedGoogle Scholar
  92. 92.
    Tajmir P, Ceddia RB, Li RK et al (2004) Leptin increases cardiomyocyte hyperplasia via extracellular signal-regulated kinase and phosphatidylinositol 3-kinase-dependent signaling pathways. Endocrinology 145:1550–1555PubMedGoogle Scholar
  93. 93.
    Barouch LA, Gao D, Chen L et al (2006) Cardiac myocyte apoptosis is associated with increased DNA damage and decreased survival in murine models of obesity. Circ Res 98:119–124PubMedGoogle Scholar
  94. 94.
    Matsuzawa Y, Funahashi T, Kihara S, Shimomura I (2004) Adiponectin and metabolic syndrome. Arterioscler Thromb Vasc Biol 24:29–33PubMedGoogle Scholar
  95. 95.
    Ryo M, Nakamura T, Kihara S et al (2004) Adiponectin as a biomarker of the metabolic syndrome. Circ J 68:975–981PubMedGoogle Scholar
  96. 96.
    Bruun JM, Lihn AS, Verdich C et al (2003) Regulation of adiponectin by adipose tissue-­derived cytokines: in vivo and in vitro investigations in humans. Am J Physiol Endocrinol Metab 285(3):E527–E533PubMedGoogle Scholar
  97. 97.
    Motoshima H, Wu X, Mahadev K et al (2004) Adiponectin suppresses proliferation and superoxide generation and enhances eNOS activity in endothelial cells treated with oxidized LDL. Biochem Biophys Res Commun 315:264–271PubMedGoogle Scholar
  98. 98.
    Wang Y, Lam KS, Xu JY et al (2005) Adiponectin inhibits cell proliferation by interacting with several growth factors in an oligomerization-dependent manner. J Biol Chem 280:18341–18347PubMedGoogle Scholar
  99. 99.
    Niu K, Asada M, Okazaki T et al (2012) Adiponectin pathway attenuates malignant mesothelioma cell growth. Am J Respir Cell Mol Biol 46:515–523PubMedGoogle Scholar
  100. 100.
    Wang Y, Lam JB, Lam KS et al (2006) Adiponectin modulates the glycogen synthase kinase-­3beta/beta-catenin signaling pathway and attenuates mammary tumorigenesis of MDA-MB-231 cells in nude mice. Cancer Res 66:11462–11470PubMedGoogle Scholar
  101. 101.
    Zhang D, Guo M, Zhang W et al (2011) Adiponectin stimulates proliferation of adult hippocampal neural stem/progenitor cells through activation of p38 mitogen-activated protein kinase [p38MAPK]/glycogen synthase kinase 3β [GSK-3β]/β-catenin signaling cascade. J Biol Chem 286:44913–44920PubMedGoogle Scholar
  102. 102.
    Chen MJ, Yeh YT, Lee KT et al (2012) The promoting effect of adiponectin in hepatocellular carcinoma. J Surg Oncol 106:181–187PubMedGoogle Scholar
  103. 103.
    Lautamäki R, Rönnemaa T, Huupponen R et al (2007) Low serum adiponectin is associated with high circulating oxidized low-density lipoprotein in patients with type 2 diabetes mellitus and coronary artery disease. Metabolism 56:881–886PubMedGoogle Scholar
  104. 104.
    Kaur S, Zilmer K, Leping V et al (2011) The levels of adiponectin and leptin and their relation to other markers of cardiovascular risk in patients with psoriasis. J Eur Acad Dermatol Venereol 25:1328–1333PubMedGoogle Scholar
  105. 105.
    Porreca E, Di Febbo C, Moretta V et al (2004) Circulating leptin is associated with oxidized LDL in postmenopausal women. Atherosclerosis 175:139–143PubMedGoogle Scholar
  106. 106.
    Nakhjavani M, Morteza A, Asgarani F et al (2011) Metformin restores the correlation between serum-oxidized LDL and leptin levels in type 2 diabetic patients. Redox Rep 16:193–200PubMedGoogle Scholar
  107. 107.
    Takanabe-Mori R, Ono K, Sowa N et al (2010) Lectin-like oxidized low-density lipoprotein receptor-1 is required for the adipose tissue expression of proinflammatory cytokines in high-­fat diet-induced obese mice. Biochem Biophys Res Commun 398:576–580PubMedGoogle Scholar
  108. 108.
    Masella R, Varì R, D’Archivio M et al (2006) Oxidised LDL modulate adipogenesis in 3T3-­L1 preadipocytes by affecting the balance between cell proliferation and differentiation. FEBS Lett 580:2421–2429PubMedGoogle Scholar
  109. 109.
    Chui PC, Guan HP, Lehrke M et al (2005) PPARgamma regulates adipocyte cholesterol metabolism via oxidized LDL receptor 1. J Clin Invest 115:2244–2256PubMedGoogle Scholar
  110. 110.
    Scazzocchio B, Varì R, D’Archivio M et al (2009) Oxidized LDL impair adipocyte response to insulin by activating serine/threonine kinases. J Lipid Res 50(5):832–845PubMedGoogle Scholar
  111. 111.
    Scoles DR, Xu X, Wang H et al (2010) Liver X receptor agonist inhibits proliferation of ovarian carcinoma cells stimulated by oxidized low density lipoprotein. Gynecol Oncol 116:109–116PubMedGoogle Scholar
  112. 112.
    Dandapat A, Hu C, Sun L et al (2007) Small concentrations of ox-LDL induce capillary tube formation from endothelial cells via LOX-1-dependent redox-sensitive pathway. Arterioscler Thromb Vasc Biol 27:2435–2442PubMedGoogle Scholar
  113. 113.
    Mehta JL (2004) The role of LOX-1, a novel lectin-like receptor for oxidized low density lipoprotein in atherosclerosis. Can J Cardiol 20(suppl B):32B–36BPubMedGoogle Scholar
  114. 114.
    Watanabe T, Pakala R, Katagiri T et al (2002) Lysophosphatidylcholine is a major contributor to the synergistic effect of mildly oxidized low-density lipoprotein with endothelin-1 on vascular smooth muscle cell proliferation. J Cardiovasc Pharmacol 39:449–459PubMedGoogle Scholar
  115. 115.
    Stiko A, Regnström J, Shah PK et al (1996) Active oxygen species and lysophosphatidylcholine are involved in oxidized low density lipoprotein activation of smooth muscle cell DNA synthesis. Arterioscler Thromb Vasc Biol 16:194–200PubMedGoogle Scholar
  116. 116.
    Bochkov VN, Philippova M, Oskolkova O et al (2006) Oxidized phospholipids stimulate angiogenesis via autocrine mechanisms, implicating a novel role for lipid oxidation in the evolution of atherosclerotic lesions. Circ Res 99:900–908PubMedGoogle Scholar
  117. 117.
    Davies SS, Pontsler AV, Marathe GK et al (2001) Oxidized alkyl phospholipids are specific, high affinity peroxisome proliferator-activated receptor gamma ligands and agonists. J Biol Chem 276:16015–16023PubMedGoogle Scholar
  118. 118.
    Auron PE (1998) The interleukin 1 receptor: ligand interactions and signal transduction. Cytokine Growth Factor Rev 9:221–237PubMedGoogle Scholar
  119. 119.
    Janssens S, Beyaert R (2003) Functional diversity and regulation of different interleukin-1 receptor-associated kinase [IRAK] family members. Mol Cell 11:293–302PubMedGoogle Scholar
  120. 120.
    Carmi Y, Voronov E, Dotan S et al (2009) The role of macrophage-derived IL-1 in induction and maintenance of angiogenesis. J Immunol 183:4705–4714PubMedGoogle Scholar
  121. 121.
    Voronov E, Carmi Y, Apte RN (2007) Role of IL-1-mediated inflammation in tumor angiogenesis. Adv Exp Med Biol 601:265–270PubMedGoogle Scholar
  122. 122.
    Jagielska J, Kapopara PR, Salguero G et al (2012) Interleukin-1 assembles a proangiogenic signaling module consisting of caveolin-1, tumor necrosis factor receptor-associated factor 6, p38-mitogen-activated protein kinase [MAPK], and MAPK-activated protein kinase 2 in endothelial cells. Arterioscler Thromb Vasc Biol 32:1280–1288PubMedGoogle Scholar
  123. 123.
    Ara T, Declerck YA (2010) Interleukin-6 in bone metastasis and cancer progression. Eur J Cancer 46:1223–1231PubMedGoogle Scholar
  124. 124.
    Fan Y, Ye J, Shen F et al (2008) Interleukin-6 stimulates circulating blood-derived endothelial progenitor cell angiogenesis in vitro. J Cereb Blood Flow Metab 28:90–98PubMedGoogle Scholar
  125. 125.
    Gertz K, Kronenberg G, Kälin RE et al (2012) Essential role of interleukin-6 in post-stroke angiogenesis. Brain 135:1964–1980PubMedGoogle Scholar
  126. 126.
    Baggiolini M, Dewald B, Moser B (1994) Interleukin-8 and related chemotactic cytokines—CXC and CC chemokines. Adv Immunol 55:97–179PubMedGoogle Scholar
  127. 127.
    Desbaillets I, Diserens AC, de Tribolet N et al (1999) Regulation of interleukin-8 expression by reduced oxygen pressure in human glioblastoma. Oncogene 18:1447–1456PubMedGoogle Scholar
  128. 128.
    Yoshida S, OnoM ST et al (1997) Involvement of interleukin-8, vascular endothelial growth factor, and basic fibroblast growth factor in tumor necrosis factor alpha-dependent angiogenesis. Mol Cell Biol 17:4015–4023PubMedGoogle Scholar
  129. 129.
    Li A, Dubey S, Varney ML et al (2003) IL-8 directly enhanced endothelial cell survival, proliferation, and matrix metalloproteinases production and regulated angiogenesis. J Immunol 170:3369–3376PubMedGoogle Scholar
  130. 130.
    Koch AE, Polverini PJ, Kunkel SL et al (1992) Interleukin-8 as a macrophage derived mediator of angiogenesis. Science 258:1798–1801PubMedGoogle Scholar
  131. 131.
    Strieter RM, Polverini PG, Kunkel SL et al (1995) The functional role of the ELR motif in CXC chemokine-mediated angiogenesis. J Biol Chem 270:27348–27357PubMedGoogle Scholar
  132. 132.
    Libby P, Ordovas JM, Auger KR et al (1986) Endotoxin and tumor necrosis factor induce interleukin-1 gene expression in adult human vascular endothelial cells. Am J Pathol 124:179–185PubMedGoogle Scholar
  133. 133.
    Hamanaka R, Kohno K, Seguchi T et al (1992) Induction of low density lipoprotein receptor and a transcription factor SP-1 by tumor necrosis factor in human microvascular endothelial cells. J Biol Chem 267:13160–13165PubMedGoogle Scholar
  134. 134.
    Lowenthal JW, Ballard DW, Bogerd H et al (1989) Tumor necrosis factor-alpha activation of the IL-2 receptor-alpha gene involves the induction of kappa B-specific DNA binding ­proteins. J Immunol 142:3121–3128PubMedGoogle Scholar
  135. 135.
    Kuwano T, Nakao S, Yamamoto H et al (2004) Cyclooxygenase 2 is a key enzyme for inflammatory cytokine-induced angiogenesis. FASEB J 18:300–310PubMedGoogle Scholar
  136. 136.
    Ghosh N, Chaki R, Mandal V et al (2010) COX-2 as a target for cancer chemotherapy. Pharmacol Rep 62:233–244PubMedGoogle Scholar
  137. 137.
    Sheng H, Shao J, Washington MK et al (2001) Prostaglandin E2 increases growth and motility of colorectal carcinoma cells. J Biol Chem 276:18075–18081PubMedGoogle Scholar
  138. 138.
    Sheng H, Shao J, Morrow JD et al (1998) Modulation of apoptosis and Bcl-2 expression by prostaglandin E2 in human colon cancer cells. Cancer Res 58:362–366PubMedGoogle Scholar
  139. 139.
    Honjo M, Nakamura K, Yamashiro K et al (2003) Lectin-like oxidized LDL receptor-1 is a cell-adhesion molecule involved in endotoxin-induced inflammation. Proc Natl Acad Sci U S A 100:1274–1279PubMedGoogle Scholar
  140. 140.
    Hayashida K, Kume N, Minami M et al (2002) Lectin-like oxidized LDL receptor-1 [LOX-1] supports adhesion of mononuclear leukocytes and a monocyte-like cell line THP-1 cells under static and flow conditions. FEBS Lett 511:133–138PubMedGoogle Scholar
  141. 141.
    Sawamura T, Kume N, Aoyama T et al (1997) An endothelial receptor for oxidized low-­density lipoprotein. Nature 386:73–77PubMedGoogle Scholar
  142. 142.
    Deshmane SL, Kremlev S, Amini S et al (2009) Monocyte chemoattractant protein-1 [MCP-­1]: an overview. J Interferon Cytokine Res 29:313–326PubMedGoogle Scholar
  143. 143.
    Li D, Mehta JL (2000) Antisense to LOX-1 inhibits oxidized LDL-mediated upregulation of monocyte chemoattractant protein-1 and monocyte adhesion to human coronary artery endothelial cells. Circulation 101:2889–2895PubMedGoogle Scholar
  144. 144.
    Lu Y, Cai Z, Xiao G et al (2007) Monocyte chemotactic protein-1 mediates prostate cancer-­induced bone resorption. Cancer Res 67:3646–3653PubMedGoogle Scholar
  145. 145.
    Zen K, Liu DQ, Guo YL et al (2008) CD44v4 is a major E-selectin ligand that mediates breast cancer cell transendothelial migration. PLoS One 3:e1826PubMedGoogle Scholar
  146. 146.
    Liang M, Zhang P, Fu J (2007) Up-regulation of LOX-1 expression by TNF-alpha promotes trans-endothelial migration of MDA-MB-231 breast cancer cells. Cancer Lett 258:31–37PubMedGoogle Scholar
  147. 147.
    Utsugi T, Schroit AJ, Connor J et al (1991) Elevated expression of phosphatidylserine in the outer membrane leaflet of human tumor cells and recognition by activated human blood monocytes. Cancer Res 51:3062–3068PubMedGoogle Scholar
  148. 148.
    Janas T, Janas T, Yarus M (2006) Specific RNA binding to ordered phospholipid bilayers. Nucleic Acids Res 34:2128–2136PubMedGoogle Scholar
  149. 149.
    Vickers KC, Palmisano BT, Shoucri BM et al (2011) MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins. Nat Cell Biol 13:423–433PubMedGoogle Scholar
  150. 150.
    Lovat F, Valeri N, Croce CM (2011) MicroRNAs in the pathogenesis of cancer. Semin Oncol 38:724–733PubMedGoogle Scholar
  151. 151.
    Tie J, Fan D (2011) Big roles of microRNAs in tumorigenesis and tumor development. Histol Histopathol 26:1353–1361PubMedGoogle Scholar
  152. 152.
    Zipursky SL, Sanes JR (2010) Chemoaffinity revisited: dscams, protocadherins, and neural circuit assembly. Cell 143:343–353PubMedGoogle Scholar
  153. 153.
    Novak P, Jensen T, Oshiro MM et al (2008) Agglomerative epigenetic aberrations are a common event in human breast cancer. Cancer Res 68:8616–8625PubMedGoogle Scholar
  154. 154.
    Dallosso AR, Hancock AL, Szemes M et al (2009) Frequent long-range epigenetic silencing of protocadherin gene clusters on chromosome 5q31 in Wilms’ tumor. PLoS Genet 5:e1000745PubMedGoogle Scholar
  155. 155.
    Wang C, Yu G, Liu J et al (2012) Downregulation of PCDH9 predicts prognosis for patients with glioma. J Clin Neurosci 19:541–545PubMedGoogle Scholar
  156. 156.
    Li Z, Chim JC, Yang M et al (2012) Role of PCDH10 and its hypermethylation in human gastric cancer. Biochim Biophys Acta 1823:298–305PubMedGoogle Scholar
  157. 157.
    Ying J, Li H, Seng TJ et al (2006) Functional epigenetics identifies a protocadherin PCDH10 as a candidate tumor suppressor for nasopharyngeal, esophageal and multiple other carcinomas with frequent methylation. Oncogene 25:1070–1080PubMedGoogle Scholar
  158. 158.
    Ying J, Gao Z, Li H et al (2007) Frequent epigenetic silencing of protocadherin 10 by methylation in multiple haematologic malignancies. Br J Haematol 136:829–832PubMedGoogle Scholar
  159. 159.
    Yu JS, Koujak S, Nagase S et al (2008) PCDH8, the human homolog of PAPC, is a candidate tumor suppressor of breast cancer. Oncogene 27:4657–4665PubMedGoogle Scholar
  160. 160.
    Narayan G, Freddy AJ, Xie D et al (2011) Promoter methylation-mediated inactivation of PCDH10 in acute lymphoblastic leukemia contributes to chemotherapy resistance. Genes Chromosomes Cancer 50:1043–1053PubMedGoogle Scholar
  161. 161.
    Dallosso AR, Oster B, Greenhough A et al (2012) Long-range epigenetic silencing of chromosome 5q31 protocadherins is involved in early and late stages of colorectal tumorigenesis through modulation of oncogenic pathways. Oncogene 31:4406–4419Google Scholar
  162. 162.
    Qin B, Xiao B, Liang D et al (2011) MicroRNAs expression in ox-LDL treated HUVECs: MiR-365 modulates apoptosis and Bcl-2 expression. Biochem Biophys Res Commun 410:127–133PubMedGoogle Scholar
  163. 163.
    Chen T, Yan H, Li Z et al (2011) MicroRNA-155 regulates lipid uptake, adhesion/chemokine marker secretion and SCG2 expression in oxLDL-stimulated dendritic cells/macrophages. Int J Cardiol 147:446–447PubMedGoogle Scholar
  164. 164.
    Chen T, Li Z, Jing T et al (2011) MicroRNA-146a regulates the maturation process and pro-­inflammatory cytokine secretion by targeting CD40L in oxLDL-stimulated dendritic cells. FEBS Lett 585:567–573PubMedGoogle Scholar
  165. 165.
    Huang RS, Hu GQ, Lin B et al (2010) MicroRNA-155 silencing enhances inflammatory response and lipid uptake in oxidized low-density lipoprotein-stimulated human THP-1 ­macrophages. J Investig Med 58:961–967PubMedGoogle Scholar
  166. 166.
    Chen KC, Hsieh IC, Hsi E et al (2011) Negative feedback regulation between microRNA let-7g and the oxLDL receptor LOX-1. J Cell Sci 124:4115–4124PubMedGoogle Scholar
  167. 167.
    Li D, Yang P, Xiong Q et al (2010) MicroRNA-125a/b-5p inhibits endothelin-1 expression in vascular endothelial cells. J Hypertens 28:1646–1654PubMedGoogle Scholar
  168. 168.
    Chen KC, Wang YS, Hu CY et al (2011) OxLDL up-regulates microRNA-29b, leading to epigenetic modifications of MMP-2/MMP-9 genes: a novel mechanism for cardiovascular diseases. FASEB J 25:1718–1728PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Division of Cardiovascular MedicineUniversity of Arkansas for Medical Sciences and the Central Arkansas Veterans Healthcare SystemLittle RockUSA

Personalised recommendations