Skip to main content
SpringerLink
Log in

Potential Mechanisms Linking Oxidized LDL to Susceptibility to Cancer

  • Chapter
  • First Online:
Biochemical Basis and Therapeutic Implications of Angiogenesis

Part of the book series: Advances in Biochemistry in Health and Disease ((ABHD,volume 6))

  • 1786 Accesses

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.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 179.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  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 371:569–578

    PubMed  Google Scholar 

  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 46:2581–2592

    PubMed  Google Scholar 

  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 348:1625–1638

    PubMed  Google Scholar 

  4. Grek CL, Tew KD (2010) Redox metabolism and malignancy. Curr Opin Pharmacol 4:362–368

    Google Scholar 

  5. Trinchieri G (2012) Cancer and inflammation: an old intuition with rapidly evolving new concepts. Annu Rev Immunol 30:677–706

    PubMed  CAS  Google Scholar 

  6. Kelesidis I, Kelesidis T, Mantzoros CS (2006) Adiponectin and cancer: a systematic review. Br J Cancer 94:1221–1225

    PubMed  CAS  Google Scholar 

  7. Braun S, Bitton-Worms K, LeRoith D (2011) The link between the metabolic syndrome and cancer. Int J Biol Sci 7:1003–1015

    PubMed  CAS  Google Scholar 

  8. Wang D, Dubois RN (2012) The role of the PGE2-aromatase pathway in obesity-associated breast inflammation. Cancer Discov 2:308–310

    PubMed  CAS  Google Scholar 

  9. Brown MS, Kovanen PT, Goldstein JL (1981) Regulation of plasma cholesterol by lipoprotein receptors. Science 212:628–635

    PubMed  CAS  Google Scholar 

  10. Vykhovanets EV, Shankar E, Vykhovanets OV et al (2011) High-fat diet increases NF-κB signaling in the prostate of reporter mice. Prostate 71:147–156

    PubMed  CAS  Google Scholar 

  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 51:883–896

    PubMed  Google Scholar 

  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) 16:1454–1456

    CAS  Google Scholar 

  13. Holvoet P (2008) Relations between metabolic syndrome, oxidative stress and inflammation and cardiovascular disease. Verh K Acad Geneeskd Belg 70:193–219

    PubMed  CAS  Google Scholar 

  14. Holvoet P, Lee DH, Steffes M et al (2008) Association between circulating oxidized low-­density lipoprotein and incidence of the metabolic syndrome. JAMA 299:2287–2293

    PubMed  CAS  Google Scholar 

  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 53:1068–1073

    PubMed  CAS  Google Scholar 

  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 112:651–657

    PubMed  CAS  Google Scholar 

  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 320:915–924

    PubMed  CAS  Google Scholar 

  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 79:1712–1716

    PubMed  CAS  Google Scholar 

  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 84:537–540

    PubMed  CAS  Google Scholar 

  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 20:1116–1122

    PubMed  CAS  Google Scholar 

  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 947:224–228

    PubMed  CAS  Google Scholar 

  22. Marnett LJ (1999) Chemistry and biology of DNA damage by malondialdehyde. IARC Sci Publ 150:17–27

    PubMed  CAS  Google Scholar 

  23. Esterbauer H, Schaur RJ, Zollner H (1991) Chemistry and biochemistry of 4-­hydroxynonenal, malonaldehyde and related aldehydes. Free Radic Biol Med 11(1):81–128

    PubMed  CAS  Google Scholar 

  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 101:8598–8602

    PubMed  CAS  Google Scholar 

  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 21:1017–1022

    PubMed  CAS  Google Scholar 

  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 283:19456–19464

    CAS  Google Scholar 

  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 305:115–121

    PubMed  CAS  Google Scholar 

  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 104:1767–1772

    PubMed  CAS  Google Scholar 

  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 104:210–218

    PubMed  CAS  Google Scholar 

  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 45:1013–1023

    PubMed  CAS  Google Scholar 

  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–H1787

    PubMed  CAS  Google Scholar 

  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–H861

    PubMed  CAS  Google Scholar 

  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 30:436–441

    PubMed  CAS  Google Scholar 

  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–H2308

    PubMed  CAS  Google Scholar 

  35. Jiang F, Lim HK, Morris MJ et al (2011) Systemic upregulation of NADPH oxidase in diet-­induced obesity in rats. Redox Rep 16:223–229

    PubMed  CAS  Google Scholar 

  36. Kamata T (2009) Roles of Nox1 and other Nox isoforms in cancer development. Cancer Sci 100:1382–1388

    PubMed  CAS  Google Scholar 

  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 8:1447–1459

    PubMed  CAS  Google Scholar 

  38. Mitsushita J, Lambeth JD, Kamata T (2004) The superoxide-generating oxidase Nox1 is functionally required for Ras oncogene transformation. Cancer Res 64:3580–3585

    PubMed  CAS  Google Scholar 

  39. Irani K, Xia Y, Zweier JL et al (1997) Mitogenic signaling mediated by oxidants in Ras-­transformed fibroblasts. Science 275:1649–1652

    PubMed  CAS  Google Scholar 

  40. Suh YA, Arnold RS, Lassegue B et al (1999) Cell transformation by the superoxide-­generating oxidase Mox1. Nature 401:79–82

    PubMed  CAS  Google Scholar 

  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 48:1338–1346

    PubMed  CAS  Google Scholar 

  42. Graham KA, Kulawiec M, Owens KM et al (2010) NADPH oxidase 4 is an oncoprotein loc.lized to mitochondria. Cancer Biol Ther 10:223–231

    PubMed  CAS  Google Scholar 

  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–E98

    PubMed  Google Scholar 

  44. Nowsheen S, Aziz K, Kryston TB et al (2012) The interplay between inflammation and oxidative stress in carcinogenesis. Curr Mol Med 12:672–680

    PubMed  CAS  Google Scholar 

  45. Reedy J (1975) Galen on cancer and related diseases. Clio Med 10:227–238

    PubMed  CAS  Google Scholar 

  46. Balkwill F, Mantovani A (2001) Inflammation and cancer: back to Virchow? Lancet 357:539–545

    PubMed  CAS  Google Scholar 

  47. Norris AL, Steinberger J, Steffen LM et al (2011) Circulating oxidized LDL and inflammation in extreme pediatric obesity. Obesity (Silver Spring) 19:1415–1419

    CAS  Google Scholar 

  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 22:1162–1167

    PubMed  CAS  Google Scholar 

  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 64:1024–1034

    PubMed  CAS  Google Scholar 

  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 275:12633–12638

    PubMed  CAS  Google Scholar 

  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 303:313–319

    PubMed  CAS  Google Scholar 

  52. http://www.bu.edu/nf-kb/gene-resources

  53. Rayet B, Gélinas C (1999) Aberrant rel/nfkb genes and activity in human cancer. Oncogene 18:6938–6947

    PubMed  CAS  Google Scholar 

  54. Sun XF, Zhang H (2007) NFKB and NFKBI polymorphisms in relation to susceptibility of tumour and other diseases. Histol Histopathol 22:1387–1398

    PubMed  CAS  Google Scholar 

  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 17:348–356

    PubMed  CAS  Google Scholar 

  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 379:395–399

    PubMed  CAS  Google Scholar 

  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):e20277

    PubMed  CAS  Google Scholar 

  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 39:1201–1207

    PubMed  CAS  Google Scholar 

  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 18:884–893

    PubMed  CAS  Google Scholar 

  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 12:568–576

    PubMed  Google Scholar 

  61. Fajardo LF, Kwan HH, Kowalski J et al (1992) Dual role of tumor necrosis factor-alpha in angiogenesis. Am J Pathol 140:539–544

    PubMed  CAS  Google Scholar 

  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 13:3301–3310

    PubMed  CAS  Google Scholar 

  63. Moore RJ, Owens DM, Stamp G et al (1999) Mice deficient in tumor necrosis factor-alpha are resistant to skin carcinogenesis. Nat Med 5:828–831

    PubMed  CAS  Google Scholar 

  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 71:6965–6975

    PubMed  CAS  Google Scholar 

  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:e21

    PubMed  CAS  Google Scholar 

  66. Heikkilä K, Ebrahim S, Lawlor DA (2008) Systematic review of the association between circulating interleukin-6 [IL-6] and cancer. Eur J Cancer 44:937–945

    PubMed  Google Scholar 

  67. Kishimoto T (2005) Interleukin-6: from basic science to medicine–40 years in immunology. Annu Rev Immunol 23:1–21

    PubMed  CAS  Google Scholar 

  68. Becker C, Fantini MC, Wirtz S et al (2005) IL-6 signaling promotes tumor growth in colorectal cancer. Cell Cycle 4:217–220

    PubMed  CAS  Google Scholar 

  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 323:155–160

    PubMed  CAS  Google Scholar 

  70. Waugh DJJ, Wilson C (2008) The interleukin-8 pathway in cancer. Clin Cancer Res 14:6735–6741

    PubMed  CAS  Google Scholar 

  71. Kuniyasu A, Hayashi S, Nakayama H (2002) Adipocytes recognize and degrade oxidized low density lipoprotein through CD36. Biochem Biophys Res Commun 295:319–323

    PubMed  CAS  Google Scholar 

  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 14:47–53

    PubMed  CAS  Google Scholar 

  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 214:345–349

    PubMed  Google Scholar 

  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 49:304–311

    PubMed  CAS  Google Scholar 

  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 137:15–27

    PubMed  CAS  Google Scholar 

  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 9:117

    PubMed  Google Scholar 

  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 26:742–745

    PubMed  Google Scholar 

  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 97:2130–2138

    PubMed  CAS  Google Scholar 

  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 6:1573–1579

    Google Scholar 

  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 18:30–33

    PubMed  CAS  Google Scholar 

  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 216:103–108

    PubMed  CAS  Google Scholar 

  82. Costa S, Zimetti F, Pedrelli M et al (2010) Manidipine reduces pro-inflammatory cytokines secretion in human endothelial cells and macrophages. Pharmacol Res 62:265–270

    PubMed  CAS  Google Scholar 

  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–C1187

    PubMed  CAS  Google Scholar 

  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 214:357–363

    PubMed  CAS  Google Scholar 

  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 413:566–571

    PubMed  CAS  Google Scholar 

  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 45:488–495

    PubMed  CAS  Google Scholar 

  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 92:265–281

    Google Scholar 

  88. Park J, Euhus DM, Scherer PE (2011) Paracrine and endocrine effects of adipose tissue on cancer development and progression. Endocr Rev 32:550–570

    PubMed  CAS  Google Scholar 

  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 147:173–180

    PubMed  CAS  Google Scholar 

  90. Wauman J, Tavernier J (2011) Leptin receptor signaling: pathways to leptin resistance. Front Biosci 17:2771–2793

    Google Scholar 

  91. Ukropec J, Seböková E, Klimes I (2001) Nutrient sensing, leptin and insulin action. Arch Physiol Biochem 109:38–51

    PubMed  CAS  Google Scholar 

  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 145:1550–1555

    PubMed  CAS  Google Scholar 

  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 98:119–124

    PubMed  CAS  Google Scholar 

  94. Matsuzawa Y, Funahashi T, Kihara S, Shimomura I (2004) Adiponectin and metabolic syndrome. Arterioscler Thromb Vasc Biol 24:29–33

    PubMed  CAS  Google Scholar 

  95. Ryo M, Nakamura T, Kihara S et al (2004) Adiponectin as a biomarker of the metabolic syndrome. Circ J 68:975–981

    PubMed  CAS  Google Scholar 

  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–E533

    PubMed  CAS  Google Scholar 

  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 315:264–271

    PubMed  CAS  Google Scholar 

  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 280:18341–18347

    PubMed  CAS  Google Scholar 

  99. Niu K, Asada M, Okazaki T et al (2012) Adiponectin pathway attenuates malignant mesothelioma cell growth. Am J Respir Cell Mol Biol 46:515–523

    PubMed  CAS  Google Scholar 

  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 66:11462–11470

    PubMed  CAS  Google Scholar 

  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 286:44913–44920

    PubMed  CAS  Google Scholar 

  102. Chen MJ, Yeh YT, Lee KT et al (2012) The promoting effect of adiponectin in hepatocellular carcinoma. J Surg Oncol 106:181–187

    PubMed  CAS  Google Scholar 

  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 56:881–886

    PubMed  Google Scholar 

  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 25:1328–1333

    PubMed  CAS  Google Scholar 

  105. Porreca E, Di Febbo C, Moretta V et al (2004) Circulating leptin is associated with oxidized LDL in postmenopausal women. Atherosclerosis 175:139–143

    PubMed  CAS  Google Scholar 

  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 16:193–200

    PubMed  CAS  Google Scholar 

  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 398:576–580

    PubMed  CAS  Google Scholar 

  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 580:2421–2429

    PubMed  CAS  Google Scholar 

  109. Chui PC, Guan HP, Lehrke M et al (2005) PPARgamma regulates adipocyte cholesterol metabolism via oxidized LDL receptor 1. J Clin Invest 115:2244–2256

    PubMed  CAS  Google Scholar 

  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):832–845

    PubMed  CAS  Google Scholar 

  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 116:109–116

    PubMed  CAS  Google Scholar 

  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 27:2435–2442

    PubMed  CAS  Google Scholar 

  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–36B

    PubMed  Google Scholar 

  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 39:449–459

    PubMed  CAS  Google Scholar 

  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 16:194–200

    PubMed  CAS  Google Scholar 

  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 99:900–908

    PubMed  CAS  Google Scholar 

  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 276:16015–16023

    PubMed  CAS  Google Scholar 

  118. Auron PE (1998) The interleukin 1 receptor: ligand interactions and signal transduction. Cytokine Growth Factor Rev 9:221–237

    PubMed  CAS  Google Scholar 

  119. Janssens S, Beyaert R (2003) Functional diversity and regulation of different interleukin-1 receptor-associated kinase [IRAK] family members. Mol Cell 11:293–302

    PubMed  CAS  Google Scholar 

  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 183:4705–4714

    PubMed  CAS  Google Scholar 

  121. Voronov E, Carmi Y, Apte RN (2007) Role of IL-1-mediated inflammation in tumor angiogenesis. Adv Exp Med Biol 601:265–270

    PubMed  Google Scholar 

  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 32:1280–1288

    PubMed  CAS  Google Scholar 

  123. Ara T, Declerck YA (2010) Interleukin-6 in bone metastasis and cancer progression. Eur J Cancer 46:1223–1231

    PubMed  CAS  Google Scholar 

  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 28:90–98

    PubMed  CAS  Google Scholar 

  125. Gertz K, Kronenberg G, Kälin RE et al (2012) Essential role of interleukin-6 in post-stroke angiogenesis. Brain 135:1964–1980

    PubMed  Google Scholar 

  126. Baggiolini M, Dewald B, Moser B (1994) Interleukin-8 and related chemotactic cytokines—CXC and CC chemokines. Adv Immunol 55:97–179

    PubMed  CAS  Google Scholar 

  127. Desbaillets I, Diserens AC, de Tribolet N et al (1999) Regulation of interleukin-8 expression by reduced oxygen pressure in human glioblastoma. Oncogene 18:1447–1456

    PubMed  CAS  Google Scholar 

  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 17:4015–4023

    PubMed  CAS  Google Scholar 

  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 170:3369–3376

    PubMed  CAS  Google Scholar 

  130. Koch AE, Polverini PJ, Kunkel SL et al (1992) Interleukin-8 as a macrophage derived mediator of angiogenesis. Science 258:1798–1801

    PubMed  CAS  Google Scholar 

  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 270:27348–27357

    PubMed  CAS  Google Scholar 

  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 124:179–185

    PubMed  CAS  Google Scholar 

  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 267:13160–13165

    PubMed  CAS  Google Scholar 

  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 142:3121–3128

    PubMed  CAS  Google Scholar 

  135. Kuwano T, Nakao S, Yamamoto H et al (2004) Cyclooxygenase 2 is a key enzyme for inflammatory cytokine-induced angiogenesis. FASEB J 18:300–310

    PubMed  CAS  Google Scholar 

  136. Ghosh N, Chaki R, Mandal V et al (2010) COX-2 as a target for cancer chemotherapy. Pharmacol Rep 62:233–244

    PubMed  CAS  Google Scholar 

  137. Sheng H, Shao J, Washington MK et al (2001) Prostaglandin E2 increases growth and motility of colorectal carcinoma cells. J Biol Chem 276:18075–18081

    PubMed  CAS  Google Scholar 

  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 58:362–366

    PubMed  CAS  Google Scholar 

  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 100:1274–1279

    PubMed  CAS  Google Scholar 

  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 511:133–138

    PubMed  CAS  Google Scholar 

  141. Sawamura T, Kume N, Aoyama T et al (1997) An endothelial receptor for oxidized low-­density lipoprotein. Nature 386:73–77

    PubMed  CAS  Google Scholar 

  142. Deshmane SL, Kremlev S, Amini S et al (2009) Monocyte chemoattractant protein-1 [MCP-­1]: an overview. J Interferon Cytokine Res 29:313–326

    PubMed  CAS  Google Scholar 

  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 101:2889–2895

    PubMed  CAS  Google Scholar 

  144. Lu Y, Cai Z, Xiao G et al (2007) Monocyte chemotactic protein-1 mediates prostate cancer-­induced bone resorption. Cancer Res 67:3646–3653

    PubMed  CAS  Google Scholar 

  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:e1826

    PubMed  Google Scholar 

  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 258:31–37

    PubMed  CAS  Google Scholar 

  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 51:3062–3068

    PubMed  CAS  Google Scholar 

  148. Janas T, Janas T, Yarus M (2006) Specific RNA binding to ordered phospholipid bilayers. Nucleic Acids Res 34:2128–2136

    PubMed  CAS  Google Scholar 

  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 13:423–433

    PubMed  CAS  Google Scholar 

  150. Lovat F, Valeri N, Croce CM (2011) MicroRNAs in the pathogenesis of cancer. Semin Oncol 38:724–733

    PubMed  CAS  Google Scholar 

  151. Tie J, Fan D (2011) Big roles of microRNAs in tumorigenesis and tumor development. Histol Histopathol 26:1353–1361

    PubMed  CAS  Google Scholar 

  152. Zipursky SL, Sanes JR (2010) Chemoaffinity revisited: dscams, protocadherins, and neural circuit assembly. Cell 143:343–353

    PubMed  CAS  Google Scholar 

  153. Novak P, Jensen T, Oshiro MM et al (2008) Agglomerative epigenetic aberrations are a common event in human breast cancer. Cancer Res 68:8616–8625

    PubMed  CAS  Google Scholar 

  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:e1000745

    PubMed  Google Scholar 

  155. Wang C, Yu G, Liu J et al (2012) Downregulation of PCDH9 predicts prognosis for patients with glioma. J Clin Neurosci 19:541–545

    PubMed  CAS  Google Scholar 

  156. Li Z, Chim JC, Yang M et al (2012) Role of PCDH10 and its hypermethylation in human gastric cancer. Biochim Biophys Acta 1823:298–305

    PubMed  CAS  Google Scholar 

  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 25:1070–1080

    PubMed  CAS  Google Scholar 

  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 136:829–832

    PubMed  CAS  Google Scholar 

  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 27:4657–4665

    PubMed  CAS  Google Scholar 

  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 50:1043–1053

    PubMed  CAS  Google Scholar 

  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 31:4406–4419

    Google Scholar 

  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 410:127–133

    PubMed  CAS  Google Scholar 

  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 147:446–447

    PubMed  Google Scholar 

  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 585:567–573

    PubMed  CAS  Google Scholar 

  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 58:961–967

    PubMed  CAS  Google Scholar 

  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 124:4115–4124

    PubMed  CAS  Google Scholar 

  167. Li D, Yang P, Xiong Q et al (2010) MicroRNA-125a/b-5p inhibits endothelin-1 expression in vascular endothelial cells. J Hypertens 28:1646–1654

    PubMed  CAS  Google Scholar 

  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 25:1718–1728

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Cardiovascular Medicine, University of Arkansas for Medical Sciences and the Central Arkansas Veterans Healthcare System, 4301 West Markham, Little Rock, AR, 72205, USA

    Magomed Khaidakov & Jawahar L. Mehta

Authors
  1. Magomed Khaidakov
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jawahar L. Mehta
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Magomed Khaidakov .

Editor information

Editors and Affiliations

  1. Div. of Cardiovascular Medicine, UAMS, Little Rock, AR, USA, 4301 W Markham, Little Rock, 72205, Arkansas, USA

    Jawahar L. Mehta

  2. Institute of Cardiovascular Sciences, St. Boniface Hosp. Research, Univ. of Ma, 351 Tache Avenue, Winnipeg, R2H 2A6, Manitoba, Canada

    Naranjan S. Dhalla

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this chapter

Cite this chapter

Khaidakov, M., Mehta, J.L. (2013). Potential Mechanisms Linking Oxidized LDL to Susceptibility to Cancer. In: Mehta, J., Dhalla, N. (eds) Biochemical Basis and Therapeutic Implications of Angiogenesis. Advances in Biochemistry in Health and Disease, vol 6. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5857-9_19

Download citation

Publish with us

Policies and ethics

Search

Navigation