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Novel Adipocytokines: Monocyte Chemotactic Protein-1, Plasminogen Activator Inhibitor-1, Chemerin

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Book cover Adipocytokines, Energy Balance, and Cancer

Part of the book series: Energy Balance and Cancer ((EBAC,volume 12))

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Abstract

Given the global increase in obesity, significant research has focused on understanding the role of adipokines, or adipocytokines, on obesity-related pathologies. In the last two decades, hundreds of adipokines have been acknowledged. Monocyte chemoattractant protein (MCP) 1, chemerin, and plasminogen activator inhibitor (PAI) 1 are three such signaling molecules that have recently been classified as adipokines. Although these novel adipokines have clear roles in activities independent of obesity-related pathologies, emerging evidence now identifies their importance in metabolic-related diseases and cancer. This chapter will first provide a brief discussion on the discovery, structure, and receptors for MCP-1, chemerin, and PAI-1. Second, we will discuss the role of these novel adipocytokines on adiposity and subsequent obesity-related diseases. Finally, we will examine the available literature linking MCP-1, chemerin, and PAI-1 to tumorigenesis. Based on the literature, it is clear that these novel adipokines can impact disease pathology as related to obesity and tumorigenesis. The majority of the literature links increased expression of these adipokines to disease pathology. However, there is also evidence implicating that a decrease in these factors can influence obesity and cancer. Thus, it is possible that the role for these adipokines may be dependent on the model. Further, it is likely that the dysregulation of these novel adipokines resulting in either overexpression or underexpression results in an unfavorable outcome.

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References

  1. Gu L, Tseng SC, Rollins BJ (1999) Monocyte chemoattractant protein-1. Chem Immunol 72:7–29

    Article  CAS  PubMed  Google Scholar 

  2. Sheikine Y, Hansson GK (2004) Chemokines and atherosclerosis. Ann Med 36:98–118

    Article  CAS  PubMed  Google Scholar 

  3. Yoshimura T, Yuhki N, Moore SK, Appella E, Lerman MI, Leonard EJ (1989) Human monocyte chemoattractant protein-1 (MCP-1). Full-length cDNA cloning, expression in mitogen-stimulated blood mononuclear leukocytes, and sequence similarity to mouse competence gene JE. FEBS Lett 244:487–493

    Article  CAS  PubMed  Google Scholar 

  4. Furutani Y, Nomura H, Notake M et al (1989) Cloning and sequencing of the cDNA for human monocyte chemotactic and activating factor (MCAF). Biochem Biophys Res Commun 159:249–255

    Article  CAS  PubMed  Google Scholar 

  5. Rollins BJ, Morrison ED, Stiles CD (1988) Cloning and expression of JE, a gene inducible by platelet-derived growth factor and whose product has cytokine-like properties. Proc Natl Acad Sci U S A 85:3738–3742

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Cushing SD, Berliner JA, Valente AJ et al (1990) Minimally modified low density lipoprotein induces monocyte chemotactic protein 1 in human endothelial cells and smooth muscle cells. Proc Natl Acad Sci U S A 87:5134–5138

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Barna BP, Pettay J, Barnett GH, Zhou P, Iwasaki K, Estes ML (1994) Regulation of monocyte chemoattractant protein-1 expression in adult human non-neoplastic astrocytes is sensitive to tumor necrosis factor (TNF) or antibody to the 55-kDa TNF receptor. J Neuroimmunol 50:101–107

    Article  CAS  PubMed  Google Scholar 

  8. Standiford TJ, Kunkel SL, Phan SH, Rollins BJ, Strieter RM (1991) Alveolar macrophage-derived cytokines induce monocyte chemoattractant protein-1 expression from human pulmonary type II-like epithelial cells. J Biol Chem 266:9912–9918

    CAS  PubMed  Google Scholar 

  9. Yoshimura T, Robinson EA, Tanaka S, Appella E, Leonard EJ (1989) Purification and amino acid analysis of two human monocyte chemoattractants produced by phytohemagglutinin-stimulated human blood mononuclear leukocytes. J Immunol 142:1956–1962

    CAS  PubMed  Google Scholar 

  10. Carr MW, Roth SJ, Luther E, Rose SS, Springer TA (1994) Monocyte chemoattractant protein 1 acts as a T-lymphocyte chemoattractant. Proc Natl Acad Sci U S A 91:3652–3656

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Xu LL, Warren MK, Rose WL, Gong W, Wang JM (1996) Human recombinant monocyte chemotactic protein and other C-C chemokines bind and induce directional migration of dendritic cells in vitro. J Leukoc Biol 60:365–371

    CAS  PubMed  Google Scholar 

  12. Lodi PJ, Garrett DS, Kuszewski J et al (1994) High-resolution solution structure of the beta chemokine hMIP-1 beta by multidimensional NMR. Science 263:1762–1767

    Article  CAS  PubMed  Google Scholar 

  13. Schweickart VL, Epp A, Raport CJ, Gray PW (2000) CCR11 is a functional receptor for the monocyte chemoattractant protein family of chemokines. J Biol Chem 275:9550–9556

    Article  CAS  PubMed  Google Scholar 

  14. Patterson AM, Siddall H, Chamberlain G, Gardner L, Middleton J (2002) Expression of the duffy antigen/receptor for chemokines (DARC) by the inflamed synovial endothelium. J Pathol 197:108–116

    Article  CAS  PubMed  Google Scholar 

  15. Casarosa P, Bakker RA, Verzijl D et al (2001) Constitutive signaling of the human cytomegalovirus-encoded chemokine receptor US28. J Biol Chem 276:1133–1137

    Article  CAS  PubMed  Google Scholar 

  16. Kuhn DE, Beall CJ, Kolattukudy PE (1995) The cytomegalovirus US28 protein binds multiple CC chemokines with high affinity. Biochem Biophys Res Commun 211:325–330

    Article  CAS  PubMed  Google Scholar 

  17. Nagpal S, Patel S, Jacobe H et al (1997) Tazarotene-induced gene 2 (TIG2), a novel retinoid-responsive gene in skin. J Invest Dermatol 109:91–95

    Article  CAS  PubMed  Google Scholar 

  18. Wittamer V, Franssen JD, Vulcano M et al (2003) Specific recruitment of antigen-presenting cells by chemerin, a novel processed ligand from human inflammatory fluids. J Exp Med 198:977–985

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Zabel BA, Silverio AM, Butcher EC (2005) Chemokine-like receptor 1 expression and chemerin-directed chemotaxis distinguish plasmacytoid from myeloid dendritic cells in human blood. J Immunol 174:244–251

    Article  CAS  PubMed  Google Scholar 

  20. Zabel BA, Ohyama T, Zuniga L et al (2006) Chemokine-like receptor 1 expression by macrophages in vivo: regulation by TGF-beta and TLR ligands. Exp Hematol 34:1106–1114

    Article  CAS  PubMed  Google Scholar 

  21. Parolini S, Santoro A, Marcenaro E et al (2007) The role of chemerin in the colocalization of NK and dendritic cell subsets into inflamed tissues. Blood 109:3625–3632

    Article  CAS  PubMed  Google Scholar 

  22. Bondue B, Wittamer V, Parmentier M (2011) Chemerin and its receptors in leukocyte trafficking, inflammation and metabolism. Cytokine Growth Factor Rev 22:331–338

    Article  CAS  PubMed  Google Scholar 

  23. Migeotte I, Franssen JD, Goriely S, Willems F, Parmentier M (2002) Distribution and regulation of expression of the putative human chemokine receptor HCR in leukocyte populations. Eur J Immunol 32:494–501

    Article  CAS  PubMed  Google Scholar 

  24. Yoshimura T, Oppenheim JJ (2011) Chemokine-like receptor 1 (CMKLR1) and chemokine (C-C motif) receptor-like 2 (CCRL2); two multifunctional receptors with unusual properties. Exp Cell Res 317:674–684

    Article  CAS  PubMed  Google Scholar 

  25. Meder W, Wendland M, Busmann A et al (2003) Characterization of human circulating TIG2 as a ligand for the orphan receptor ChemR23. FEBS Lett 555:495–499

    Article  CAS  PubMed  Google Scholar 

  26. Zabel BA, Nakae S, Zuniga L et al (2008) Mast cell-expressed orphan receptor CCRL2 binds chemerin and is required for optimal induction of IgE-mediated passive cutaneous anaphylaxis. J Exp Med 205:2207–2220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Zabel BA, Zuniga L, Ohyama T et al (2006) Chemoattractants, extracellular proteases, and the integrated host defense response. Exp Hematol 34:1021–1032

    Article  CAS  PubMed  Google Scholar 

  28. Zabel BA, Allen SJ, Kulig P et al (2005) Chemerin activation by serine proteases of the coagulation, fibrinolytic, and inflammatory cascades. J Biol Chem 280:34661–34666

    Article  CAS  PubMed  Google Scholar 

  29. Dupont DM, Madsen JB, Kristensen T et al (2009) Biochemical properties of plasminogen activator inhibitor-1. Front Biosci (Landmark Ed) 14:1337–1361

    Article  CAS  Google Scholar 

  30. De Taeye B, Gils A, Declerck PJ (2004) The story of the serpin plasminogen activator inhibitor 1: is there any need for another mutant? Thromb Haemost 92:898–924

    PubMed  Google Scholar 

  31. Cesari M, Pahor M, Incalzi RA (2010) Plasminogen activator inhibitor-1 (PAI-1): a key factor linking fibrinolysis and age-related subclinical and clinical conditions. Cardiovasc Ther 28:e72–e91

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Zorio E, Gilabert-Estelles J, Espana F, Ramon LA, Cosin R, Estelles A (2008) Fibrinolysis: the key to new pathogenetic mechanisms. Curr Med Chem 15:923–929

    Article  CAS  PubMed  Google Scholar 

  33. Loskutoff DJ, van Mourik JA, Erickson LA, Lawrence D (1983) Detection of an unusually stable fibrinolytic inhibitor produced by bovine endothelial cells. Proc Natl Acad Sci U S A 80:2956–2960

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Huber J, Kiefer FW, Zeyda M et al (2008) CC chemokine and CC chemokine receptor profiles in visceral and subcutaneous adipose tissue are altered in human obesity. J Clin Endocrinol Metab 93:3215–3221

    Article  CAS  PubMed  Google Scholar 

  35. Harman-Boehm I, Bluher M, Redel H et al (2007) Macrophage infiltration into omental versus subcutaneous fat across different populations: effect of regional adiposity and the comorbidities of obesity. J Clin Endocrinol Metab 92:2240–2247

    Article  CAS  PubMed  Google Scholar 

  36. Enos RT, Davis JM, Velazquez KT et al (2013) Influence of dietary saturated fat content on adiposity, macrophage behavior, inflammation, and metabolism: composition matters. J Lipid Res 54:152–163

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Gerhardt CC, Romero IA, Cancello R, Camoin L, Strosberg AD (2001) Chemokines control fat accumulation and leptin secretion by cultured human adipocytes. Mol Cell Endocrinol 175:81–92

    Article  CAS  PubMed  Google Scholar 

  38. Meijer K, de Vries M, Al-Lahham S et al (2011) Human primary adipocytes exhibit immune cell function: adipocytes prime inflammation independent of macrophages. PLoS One 6, e17154

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr (2003) Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 112:1796–1808

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Lumeng CN, DelProposto JB, Westcott DJ, Saltiel AR (2008) Phenotypic switching of adipose tissue macrophages with obesity is generated by spatiotemporal differences in macrophage subtypes. Diabetes 57:3239–3246

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Lumeng CN, Bodzin JL, Saltiel AR (2007) Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest 117:175–184

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Bremer AA, Devaraj S, Afify A, Jialal I (2011) Adipose tissue dysregulation in patients with metabolic syndrome. J Clin Endocrinol Metab 96:E1782–E1788

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Arner E, Mejhert N, Kulyte A et al (2012) Adipose tissue microRNAs as regulators of CCL2 production in human obesity. Diabetes 61:1986–1993

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Kanda H, Tateya S, Tamori Y et al (2006) MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity. J Clin Invest 116:1494–1505

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Kamei N, Tobe K, Suzuki R et al (2006) Overexpression of monocyte chemoattractant protein-1 in adipose tissues causes macrophage recruitment and insulin resistance. J Biol Chem 281:26602–26614

    Article  CAS  PubMed  Google Scholar 

  46. Weisberg SP, Hunter D, Huber R et al (2006) CCR2 modulates inflammatory and metabolic effects of high-fat feeding. J Clin Invest 116:115–124

    Article  CAS  PubMed  Google Scholar 

  47. Amano SU, Cohen JL, Vangala P et al (2014) Local proliferation of macrophages contributes to obesity-associated adipose tissue inflammation. Cell Metab 19:162–171

    Article  CAS  PubMed  Google Scholar 

  48. Chow FY, Nikolic-Paterson DJ, Ma FY, Ozols E, Rollins BJ, Tesch GH (2007) Monocyte chemoattractant protein-1-induced tissue inflammation is critical for the development of renal injury but not type 2 diabetes in obese db/db mice. Diabetologia 50:471–480

    Article  CAS  PubMed  Google Scholar 

  49. Chen A, Mumick S, Zhang C et al (2005) Diet induction of monocyte chemoattractant protein-1 and its impact on obesity. Obes Res 13:1311–1320

    Article  CAS  PubMed  Google Scholar 

  50. Kirk EA, Sagawa ZK, McDonald TO, O’Brien KD, Heinecke JW (2008) Monocyte chemoattractant protein deficiency fails to restrain macrophage infiltration into adipose tissue [corrected]. Diabetes 57:1254–1261

    Article  CAS  PubMed  Google Scholar 

  51. Inouye KE, Shi H, Howard JK et al (2007) Absence of CC chemokine ligand 2 does not limit obesity-associated infiltration of macrophages into adipose tissue. Diabetes 56:2242–2250

    Article  CAS  PubMed  Google Scholar 

  52. Galastri S, Zamara E, Milani S et al (2012) Lack of CC chemokine ligand 2 differentially affects inflammation and fibrosis according to the genetic background in a murine model of steatohepatitis. Clin Sci (Lond) 123:459–471

    Article  CAS  Google Scholar 

  53. Cranford TL, Enos RT, Velazquez KT et al (2015) Role of MCP-1 on inflammatory processes and metabolic dysfunction following high-fat feedings in the FVB/N strain. Int J Obes (Lond) 40:844–851

    Article  CAS  Google Scholar 

  54. Fearnside JF, Dumas ME, Rothwell AR et al (2008) Phylometabonomic patterns of adaptation to high fat diet feeding in inbred mice. PLoS One 3, e1668

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Carter CP, Howles PN, Hui DY (1997) Genetic variation in cholesterol absorption efficiency among inbred strains of mice. J Nutr 127:1344–1348

    CAS  PubMed  Google Scholar 

  56. Keelan M, Hui DY, Wild G, Clandinin MT, Thomson AB (2000) Variability of the intestinal uptake of lipids is genetically determined in mice. Lipids 35:833–837

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Montgomery MK, Hallahan NL, Brown SH et al (2013) Mouse strain-dependent variation in obesity and glucose homeostasis in response to high-fat feeding. Diabetologia 56:1129–1139

    Article  CAS  PubMed  Google Scholar 

  58. Hemmrich K, Thomas GP, Abberton KM et al (2007) Monocyte chemoattractant protein-1 and nitric oxide promote adipogenesis in a model that mimics obesity. Obesity 15:2951–2957

    Article  CAS  PubMed  Google Scholar 

  59. Younce C, Kolattukudy P (2012) MCP-1 induced protein promotes adipogenesis via oxidative stress, endoplasmic reticulum stress and autophagy. Cell Physiol Biochem 30:307–320

    Article  CAS  PubMed  Google Scholar 

  60. Wernstedt Asterholm I, Tao C, Morley TS et al (2014) Adipocyte inflammation is essential for healthy adipose tissue expansion and remodeling. Cell Metab 20:103–118

    Article  CAS  PubMed  Google Scholar 

  61. Goralski KB, McCarthy TC, Hanniman EA et al (2007) Chemerin, a novel adipokine that regulates adipogenesis and adipocyte metabolism. J Biol Chem 282:28175–28188

    Article  CAS  PubMed  Google Scholar 

  62. Bozaoglu K, Bolton K, McMillan J et al (2007) Chemerin is a novel adipokine associated with obesity and metabolic syndrome. Endocrinology 148:4687–4694

    Article  CAS  PubMed  Google Scholar 

  63. Issa ME, Muruganandan S, Ernst MC et al (2012) Chemokine-like receptor 1 regulates skeletal muscle cell myogenesis. Am J Physiol Cell Physiol 302:C1621–C1631

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Ernst MC, Issa M, Goralski KB, Sinal CJ (2010) Chemerin exacerbates glucose intolerance in mouse models of obesity and diabetes. Endocrinology 151:1998–2007

    Article  CAS  PubMed  Google Scholar 

  65. Ernst MC, Haidl ID, Zuniga LA et al (2012) Disruption of the chemokine-like receptor-1 (CMKLR1) gene is associated with reduced adiposity and glucose intolerance. Endocrinology 153:672–682

    Article  CAS  PubMed  Google Scholar 

  66. Chakaroun R, Raschpichler M, Kloting N et al (2012) Effects of weight loss and exercise on chemerin serum concentrations and adipose tissue expression in human obesity. Metabolism 61:706–714

    Article  CAS  PubMed  Google Scholar 

  67. Sell H, Divoux A, Poitou C et al (2010) Chemerin correlates with markers for fatty liver in morbidly obese patients and strongly decreases after weight loss induced by bariatric surgery. J Clin Endocrinol Metab 95:2892–2896

    Article  CAS  PubMed  Google Scholar 

  68. Sell H, Laurencikiene J, Taube A et al (2009) Chemerin is a novel adipocyte-derived factor inducing insulin resistance in primary human skeletal muscle cells. Diabetes 58:2731–2740

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Weigert J, Neumeier M, Wanninger J et al (2010) Systemic chemerin is related to inflammation rather than obesity in type 2 diabetes. Clin Endocrinol (Oxf) 72:342–348

    Article  CAS  Google Scholar 

  70. Takahashi M, Okimura Y, Iguchi G et al (2011) Chemerin regulates beta-cell function in mice. Sci Rep 1:123

    PubMed  PubMed Central  Google Scholar 

  71. Muruganandan S, Parlee SD, Rourke JL, Ernst MC, Goralski KB, Sinal CJ (2011) Chemerin, a novel peroxisome proliferator-activated receptor gamma (PPARgamma) target gene that promotes mesenchymal stem cell adipogenesis. J Biol Chem 286:23982–23995

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Muruganandan S, Roman AA, Sinal CJ (2010) Role of chemerin/CMKLR1 signaling in adipogenesis and osteoblastogenesis of bone marrow stem cells. J Bone Miner Res 25:222–234

    Article  CAS  PubMed  Google Scholar 

  73. Bozaoglu K, Curran JE, Stocker CJ et al (2010) Chemerin, a novel adipokine in the regulation of angiogenesis. J Clin Endocrinol Metab 95:2476–2485

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Becker M, Rabe K, Lebherz C et al (2010) Expression of human chemerin induces insulin resistance in the skeletal muscle but does not affect weight, lipid levels, and atherosclerosis in LDL receptor knockout mice on high-fat diet. Diabetes 59:2898–2903

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Bozaoglu K, Segal D, Shields KA et al (2009) Chemerin is associated with metabolic syndrome phenotypes in a Mexican-American population. J Clin Endocrinol Metab 94:3085–3088

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Chu SH, Lee MK, Ahn KY et al (2012) Chemerin and adiponectin contribute reciprocally to metabolic syndrome. PLoS One 7, e34710

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Yang M, Yang G, Dong J et al (2010) Elevated plasma levels of chemerin in newly diagnosed type 2 diabetes mellitus with hypertension. J Investig Med 58:883–886

    Article  CAS  PubMed  Google Scholar 

  78. Yoo HJ, Choi HY, Yang SJ et al (2012) Circulating chemerin level is independently correlated with arterial stiffness. J Atheroscler Thromb 19:59–66, discussion 7-8

    Article  CAS  PubMed  Google Scholar 

  79. Yan Q, Zhang Y, Hong J et al (2012) The association of serum chemerin level with risk of coronary artery disease in Chinese adults. Endocrine 41:281–288

    Article  PubMed  CAS  Google Scholar 

  80. Hah YJ, Kim NK, Kim MK et al (2011) Relationship between chemerin levels and cardiometabolic parameters and degree of coronary stenosis in Korean patients with coronary artery disease. Diabetes Metab J 35:248–254

    Article  PubMed  PubMed Central  Google Scholar 

  81. Saremi A, Shavandi N, Parastesh M, Daneshmand H (2010) Twelve-week aerobic training decreases chemerin level and improves cardiometabolic risk factors in overweight and obese men. Asian J Sports Med 1:151–158

    Article  PubMed  PubMed Central  Google Scholar 

  82. Skurk T, Hauner H (2004) Obesity and impaired fibrinolysis: role of adipose production of plasminogen activator inhibitor-1. Int J Obes Relat Metab Disord 28:1357–1364

    Article  CAS  PubMed  Google Scholar 

  83. Sawdey MS, Loskutoff DJ (1991) Regulation of murine type 1 plasminogen activator inhibitor gene expression in vivo. Tissue specificity and induction by lipopolysaccharide, tumor necrosis factor-alpha, and transforming growth factor-beta. J Clin Invest 88:1346–1353

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Loskutoff DJ, Samad F (1998) The adipocyte and hemostatic balance in obesity: studies of PAI-1. Arterioscler Thromb Vasc Biol 18:1–6

    Article  CAS  PubMed  Google Scholar 

  85. Venugopal J, Hanashiro K, Nagamine Y (2007) Regulation of PAI-1 gene expression during adipogenesis. J Cell Biochem 101:369–380

    Article  CAS  PubMed  Google Scholar 

  86. Badawi A, Klip A, Haddad P et al (2010) Type 2 diabetes mellitus and inflammation: prospects for biomarkers of risk and nutritional intervention. Diabetes Metab Syndr Obes 3:173–186

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Birgel M, Gottschling-Zeller H, Rohrig K, Hauner H (2000) Role of cytokines in the regulation of plasminogen activator inhibitor-1 expression and secretion in newly differentiated subcutaneous human adipocytes. Arterioscler Thromb Vasc Biol 20:1682–1687

    Article  CAS  PubMed  Google Scholar 

  88. Samad F, Loskutoff DJ (1997) The fat mouse: a powerful genetic model to study elevated plasminogen activator inhibitor 1 in obesity/NIDDM. Thromb Haemost 78:652–655

    CAS  PubMed  Google Scholar 

  89. Ma LJ, Mao SL, Taylor KL et al (2004) Prevention of obesity and insulin resistance in mice lacking plasminogen activator inhibitor 1. Diabetes 53:336–346

    Article  CAS  PubMed  Google Scholar 

  90. Jankun J, Al-Senaidy A, Skrzypczak-Jankun E (2012) Can inactivators of plasminogen activator inhibitor alleviate the burden of obesity and diabetes? (Review). Int J Mol Med 29:3–11

    CAS  PubMed  Google Scholar 

  91. Correia ML, Haynes WG (2006) A role for plasminogen activator inhibitor-1 in obesity: from pie to PAI? Arterioscler Thromb Vasc Biol 26:2183–2185

    Article  CAS  PubMed  Google Scholar 

  92. Mavri A, Alessi MC, Bastelica D et al (2001) Subcutaneous abdominal, but not femoral fat expression of plasminogen activator inhibitor-1 (PAI-1) is related to plasma PAI-1 levels and insulin resistance and decreases after weight loss. Diabetologia 44:2025–2031

    Article  CAS  PubMed  Google Scholar 

  93. Hoffstedt J, Andersson IL, Persson L, Isaksson B, Arner P (2002) The common -675 4G/5G polymorphism in the plasminogen activator inhibitor-1 gene is strongly associated with obesity. Diabetologia 45:584–587

    Article  CAS  PubMed  Google Scholar 

  94. Crandall DL, Quinet EM, El Ayachi S et al (2006) Modulation of adipose tissue development by pharmacological inhibition of PAI-1. Arterioscler Thromb Vasc Biol 26:2209–2215

    Article  CAS  PubMed  Google Scholar 

  95. Festa A, Williams K, Tracy RP, Wagenknecht LE, Haffner SM (2006) Progression of plasminogen activator inhibitor-1 and fibrinogen levels in relation to incident type 2 diabetes. Circulation 113:1753–1759

    Article  CAS  PubMed  Google Scholar 

  96. Mantovani A, Sica A (2010) Macrophages, innate immunity and cancer: balance, tolerance, and diversity. Curr Opin Immunol 22:231–237

    Article  CAS  PubMed  Google Scholar 

  97. Solinas G, Germano G, Mantovani A, Allavena P (2009) Tumor-associated macrophages (TAM) as major players of the cancer-related inflammation. J Leukoc Biol 86:1065–1073

    Article  CAS  PubMed  Google Scholar 

  98. Jedinak A, Dudhgaonkar S, Sliva D (2010) Activated macrophages induce metastatic behavior of colon cancer cells. Immunobiology 215:242–249

    Article  CAS  PubMed  Google Scholar 

  99. Kaler P, Augenlicht L, Klampfer L (2009) Macrophage-derived IL-1beta stimulates Wnt signaling and growth of colon cancer cells: a crosstalk interrupted by vitamin D3. Oncogene 28:3892–3902

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Kang JC, Chen JS, Lee CH, Chang JJ, Shieh YS (2010) Intratumoral macrophage counts correlate with tumor progression in colorectal cancer. J Surg Oncol 102:242–248

    Article  CAS  PubMed  Google Scholar 

  101. Bailey C, Negus R, Morris A et al (2007) Chemokine expression is associated with the accumulation of tumour associated macrophages (TAMs) and progression in human colorectal cancer. Clin Exp Metastasis 24:121–130

    Article  CAS  PubMed  Google Scholar 

  102. Conti I, Rollins BJ (2004) CCL2 (monocyte chemoattractant protein-1) and cancer. Semin Cancer Biol 14:149–154

    Article  CAS  PubMed  Google Scholar 

  103. Ueno T, Toi M, Saji H et al (2000) Significance of macrophage chemoattractant protein-1 in macrophage recruitment, angiogenesis, and survival in human breast cancer. Clin Cancer Res 6:3282–3289

    CAS  PubMed  Google Scholar 

  104. Fujimoto H, Sangai T, Ishii G et al (2009) Stromal MCP-1 in mammary tumors induces tumor-associated macrophage infiltration and contributes to tumor progression. Int J Cancer 125:1276–1284

    Article  CAS  PubMed  Google Scholar 

  105. Saji H, Koike M, Yamori T et al (2001) Significant correlation of monocyte chemoattractant protein-1 expression with neovascularization and progression of breast carcinoma. Cancer 92:1085–1091

    Article  CAS  PubMed  Google Scholar 

  106. Soria G, Ofri-Shahak M, Haas I et al (2011) Inflammatory mediators in breast cancer: coordinated expression of TNF alpha & IL-1 beta with CCL2 & CCL5 and effects on epithelial-to-mesenchymal transition. BMC Cancer 11:130

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Soria G, Yaal-Hahoshen N, Azenshtein E et al (2008) Concomitant expression of the chemokines RANTES and MCP-1 in human breast cancer: a basis for tumor-promoting interactions. Cytokine 44:191–200

    Article  CAS  PubMed  Google Scholar 

  108. Valkovic T, Lucin K, Krstulja M, Dobi-Babic R, Jonjic N (1998) Expression of monocyte chemotactic protein-1 in human invasive ductal breast cancer. Pathol Res Pract 194:335–340

    Article  CAS  PubMed  Google Scholar 

  109. Valkovic T, Fuckar D, Stifter S et al (2005) Macrophage level is not affected by monocyte chemotactic protein-1 in invasive ductal breast carcinoma. J Cancer Res Clin Oncol 131:453–458

    Article  CAS  PubMed  Google Scholar 

  110. Dwyer RM, Potter-Beirne SM, Harrington KA et al (2007) Monocyte chemotactic protein-1 secreted by primary breast tumors stimulates migration of mesenchymal stem cells. Clin Cancer Res 13:5020–5027

    Article  CAS  PubMed  Google Scholar 

  111. Goede V, Brogelli L, Ziche M, Augustin HG (1999) Induction of inflammatory angiogenesis by monocyte chemoattractant protein-1. Int J Cancer 82:765–770

    Article  CAS  PubMed  Google Scholar 

  112. Kulbe H, Levinson NR, Balkwill F, Wilson JL (2004) The chemokine network in cancer—much more than directing cell movement. Int J Dev Biol 48:489–496

    Article  CAS  PubMed  Google Scholar 

  113. Luboshits G, Shina S, Kaplan O et al (1999) Elevated expression of the CC chemokine regulated on activation, normal T cell expressed and secreted (RANTES) in advanced breast carcinoma. Cancer Res 59:4681–4687

    CAS  PubMed  Google Scholar 

  114. Balkwill F (2004) Cancer and the chemokine network. Nat Rev Cancer 4:540–550

    Article  CAS  PubMed  Google Scholar 

  115. Popivanova BK, Kostadinova FI, Furuichi K et al (2009) Blockade of a chemokine, CCL2, reduces chronic colitis-associated carcinogenesis in mice. Cancer Res 69:7884–7892

    Article  CAS  PubMed  Google Scholar 

  116. McClellan JL, Davis JM, Steiner JL et al (2012) Intestinal inflammatory cytokine response in relation to tumorigenesis in the Apc(Min/+) mouse. Cytokine 57:113–119

    Article  CAS  PubMed  Google Scholar 

  117. McClellan JL, Davis JM, Steiner JL et al (2012) Linking tumor-associated macrophages, inflammation, and intestinal tumorigenesis: role of MCP-1. Am J Physiol Gastrointest Liver Physiol 303:G1087–G1095

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Zhao L, Lim SY, Gordon-Weeks AN et al (2013) Recruitment of a myeloid cell subset (CD11b/Gr1 mid) via CCL2/CCR2 promotes the development of colorectal cancer liver metastasis. Hepatology 57:829–839

    Article  CAS  PubMed  Google Scholar 

  119. Steiner JL, Davis JM, McClellan JL, Guglielmotti A, Murphy EA (2014) Effects of the MCP-1 synthesis inhibitor bindarit on tumorigenesis and inflammatory markers in the C3(1)/SV40Tag mouse model of breast cancer. Cytokine 66:60–68

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Coffelt SB, Hughes R, Lewis CE (2009) Tumor-associated macrophages: effectors of angiogenesis and tumor progression. Biochim Biophys Acta 1796:11–18

    CAS  PubMed  Google Scholar 

  121. Pollard JW (2008) Macrophages define the invasive microenvironment in breast cancer. J Leukoc Biol 84:623–630

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Hembruff SL, Cheng N (2009) Chemokine signaling in cancer: implications on the tumor microenvironment and therapeutic targeting. Cancer Ther 7:254–267

    CAS  PubMed  PubMed Central  Google Scholar 

  123. Bolat F, Kayaselcuk F, Nursal TZ, Yagmurdur MC, Bal N, Demirhan B (2006) Microvessel density, VEGF expression, and tumor-associated macrophages in breast tumors: correlations with prognostic parameters. J Exp Clin Cancer Res 25:365–372

    CAS  PubMed  Google Scholar 

  124. Erdogan S, Yilmaz FM, Yazici O et al (2016) Inflammation and chemerin in colorectal cancer. Tumour Biol 37:6337–42

    Article  CAS  PubMed  Google Scholar 

  125. Zhang J, Jin HC, Zhu AK, Ying RC, Wei W, Zhang FJ (2014) Prognostic significance of plasma chemerin levels in patients with gastric cancer. Peptides 61:7–11

    Article  CAS  PubMed  Google Scholar 

  126. Wang C, Wu WK, Liu X et al (2014) Increased serum chemerin level promotes cellular invasiveness in gastric cancer: a clinical and experimental study. Peptides 51:131–138

    Article  CAS  PubMed  Google Scholar 

  127. Wang N, Wang QJ, Feng YY, Shang W, Cai M (2014) Overexpression of chemerin was associated with tumor angiogenesis and poor clinical outcome in squamous cell carcinoma of the oral tongue. Clin Oral Investig 18:997–1004

    Article  PubMed  Google Scholar 

  128. Pachynski RK, Zabel BA, Kohrt HE et al (2012) The chemoattractant chemerin suppresses melanoma by recruiting natural killer cell antitumor defenses. J Exp Med 209:1427–1435

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Lin W, Chen YL, Jiang L, Chen JK (2011) Reduced expression of chemerin is associated with a poor prognosis and a lowed infiltration of both dendritic cells and natural killer cells in human hepatocellular carcinoma. Clin Lab 57:879–885

    CAS  PubMed  Google Scholar 

  130. Imai K, Takai K, Hanai T et al (2014) Impact of serum chemerin levels on liver functional reserves and platelet counts in patients with hepatocellular carcinoma. Int J Mol Sci 15:11294–11306

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  131. Kumar JD, Holmberg C, Balabanova S et al (2015) Mesenchymal stem cells exhibit regulated exocytosis in response to Chemerin and IGF. PLoS One 10, e0141331

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  132. Duffy MJ, McGowan PM, Harbeck N, Thomssen C, Schmitt M (2014) uPA and PAI-1 as biomarkers in breast cancer: validated for clinical use in level-of-evidence-1 studies. Breast Cancer Res 16:428

    Article  PubMed  PubMed Central  Google Scholar 

  133. Harms W, Malter W, Kramer S, Drebber U, Drzezga A, Schmidt M (2014) Clinical significance of urokinase-type plasminogen activator (uPA) and its type-1 inhibitor (PAI-1) for metastatic sentinel lymph node involvement in breast cancer. Anticancer Res 34:4457–4462

    CAS  PubMed  Google Scholar 

  134. Ferroni P, Roselli M, Portarena I et al (2014) Plasma plasminogen activator inhibitor-1 (PAI-1) levels in breast cancer—relationship with clinical outcome. Anticancer Res 34:1153–1161

    PubMed  Google Scholar 

  135. Magnussen S, Rikardsen OG, Hadler-Olsen E, Uhlin-Hansen L, Steigen SE, Svineng G (2014) Urokinase plasminogen activator receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1) are potential predictive biomarkers in early stage oral squamous cell carcinomas (OSCC). PLoS One 9, e101895

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  136. Chen S, Tai H, Tong X et al (2014) Variation and prognostic value of serum plasminogen activator inhibitor-1 before and after chemotherapy in patients with epithelial ovarian cancer. J Obstet Gynaecol Res 40:2058–2065

    Article  CAS  PubMed  Google Scholar 

  137. Chen H, Peng H, Liu W et al (2015) Silencing of plasminogen activator inhibitor-1 suppresses colorectal cancer progression and liver metastasis. Surgery 158:1704–1713

    Article  PubMed  Google Scholar 

  138. Gillespie E, Leeman SE, Watts LA et al (2013) Plasminogen activator inhibitor-1 is increased in colonic epithelial cells from patients with colitis-associated cancer. J Crohns Colitis 7:403–411

    Article  PubMed  Google Scholar 

  139. Bajou K, Masson V, Gerard RD et al (2001) The plasminogen activator inhibitor PAI-1 controls in vivo tumor vascularization by interaction with proteases, not vitronectin. Implications for antiangiogenic strategies. J Cell Biol 152:777–784

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Bajou K, Noel A, Gerard RD et al (1998) Absence of host plasminogen activator inhibitor 1 prevents cancer invasion and vascularization. Nat Med 4:923–928

    Article  CAS  PubMed  Google Scholar 

  141. Romer MU, Kirkebjerg Due A, Knud Larsen J et al (2005) Indication of a role of plasminogen activator inhibitor type I in protecting murine fibrosarcoma cells against apoptosis. Thromb Haemost 94:859–866

    PubMed  Google Scholar 

  142. Romer MU, Larsen L, Offenberg H, Brunner N, Lademann UA (2008) Plasminogen activator inhibitor 1 protects fibrosarcoma cells from etoposide-induced apoptosis through activation of the PI3K/Akt cell survival pathway. Neoplasia 10:1083–1091

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  143. Gutierrez LS, Schulman A, Brito-Robinson T, Noria F, Ploplis VA, Castellino FJ (2000) Tumor development is retarded in mice lacking the gene for urokinase-type plasminogen activator or its inhibitor, plasminogen activator inhibitor-1. Cancer Res 60:5839–5847

    CAS  PubMed  Google Scholar 

  144. Bajou K, Peng H, Laug WE et al (2008) Plasminogen activator inhibitor-1 protects endothelial cells from FasL-mediated apoptosis. Cancer Cell 14:324–334

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Fang H, Placencio VR, DeClerck YA (2012) Protumorigenic activity of plasminogen activator inhibitor-1 through an antiapoptotic function. J Natl Cancer Inst 104:1470–1484

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. McMahon GA, Petitclerc E, Stefansson S et al (2001) Plasminogen activator inhibitor-1 regulates tumor growth and angiogenesis. J Biol Chem 276:33964–33968

    Article  CAS  PubMed  Google Scholar 

  147. Maillard C, Jost M, Romer MU et al (2005) Host plasminogen activator inhibitor-1 promotes human skin carcinoma progression in a stage-dependent manner. Neoplasia 7:57–66

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Fen Li C, Kandel C, Baliko F, Nadesan P, Brunner N, Alman BA (2005) Plasminogen activator inhibitor-1 (PAI-1) modifies the formation of aggressive fibromatosis (desmoid tumor). Oncogene 24:1615–1624

    Article  PubMed  CAS  Google Scholar 

  149. Almholt K, Nielsen BS, Frandsen TL, Brunner N, Dano K, Johnsen M (2003) Metastasis of transgenic breast cancer in plasminogen activator inhibitor-1 gene-deficient mice. Oncogene 22:4389–4397

    Article  CAS  PubMed  Google Scholar 

  150. Placencio VR, DeClerck YA (2015) Plasminogen activator inhibitor-1 in cancer: rationale and insight for future therapeutic testing. Cancer Res 75:2969–2974

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Devy L, Blacher S, Grignet-Debrus C et al (2002) The pro- or antiangiogenic effect of plasminogen activator inhibitor 1 is dose dependent. FASEB J 16:147–154

    Article  CAS  PubMed  Google Scholar 

  152. Valiente M, Obenauf AC, Jin X et al (2014) Serpins promote cancer cell survival and vascular co-option in brain metastasis. Cell 156:1002–1016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Balsara RD, Castellino FJ, Ploplis VA (2006) A novel function of plasminogen activator inhibitor-1 in modulation of the AKT pathway in wild-type and plasminogen activator inhibitor-1-deficient endothelial cells. J Biol Chem 281:22527–22536

    Article  CAS  PubMed  Google Scholar 

  154. Schneider DJ, Chen Y, Sobel BE (2008) The effect of plasminogen activator inhibitor type 1 on apoptosis. Thromb Haemost 100:1037–1040

    CAS  PubMed  Google Scholar 

  155. Mutoh M, Niho N, Komiya M et al (2008) Plasminogen activator inhibitor-1 (Pai-1) blockers suppress intestinal polyp formation in Min mice. Carcinogenesis 29:824–829

    Article  CAS  PubMed  Google Scholar 

  156. Masuda T, Hattori N, Senoo T et al (2013) SK-216, an inhibitor of plasminogen activator inhibitor-1, limits tumor progression and angiogenesis. Mol Cancer Ther 12:2378–2388

    Article  CAS  PubMed  Google Scholar 

  157. Gomes-Giacoia E, Miyake M, Goodison S, Rosser CJ (2013) Targeting plasminogen activator inhibitor-1 inhibits angiogenesis and tumor growth in a human cancer xenograft model. Mol Cancer Ther 12:2697–2708

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Murphy, E.A. (2017). Novel Adipocytokines: Monocyte Chemotactic Protein-1, Plasminogen Activator Inhibitor-1, Chemerin. In: Reizes, O., Berger, N. (eds) Adipocytokines, Energy Balance, and Cancer. Energy Balance and Cancer, vol 12. Springer, Cham. https://doi.org/10.1007/978-3-319-41677-9_8

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