Top

Current Obesity Reports

Published in:

01-12-2018 | Metabolism (M Dalamaga, Section Editor)

Classic and Novel Adipocytokines at the Intersection of Obesity and Cancer: Diagnostic and Therapeutic Strategies

Authors: Nikolaos Spyrou, Konstantinos I. Avgerinos, Christos S. Mantzoros, Maria Dalamaga

Published in: Current Obesity Reports | Issue 4/2018

Abstract

Purpose of Review

In this review, we investigate the role of classic and novel adipocytokines in cancer pathogenesis synopsizing the mechanisms underlying the association between adipocytokines and malignancy. Special emphasis is given on novel adipocytokines as new evidence is emerging regarding their entanglement in neoplastic development.

Recent Findings

Recent data have emphasized the role of the triad of overweight/obesity, insulin resistance and adipocytokines in cancer. In the setting of obesity, classic and novel adipocytokines present independent and joint effects on activation of major intracellular signaling pathways implicated in cell proliferation, expansion, survival, adhesion, invasion, and metastasis. Until now, more than 15 adipocytokines have been associated with cancer, and this list continues to expand. While the plethora of circulating pro-inflammatory adipocytokines, such as leptin, resistin, extracellular nicotinamide phosphoribosyl transferase, and chemerin are elevated in malignancies, some adipocytokines such as adiponectin and omentin-1 are generally decreased in cancers and are considered protective against carcinogenesis.

Summary

Elucidating the intertwining of inflammation, cellular bioenergetics, and adiposopathy is significant for the development of preventive, diagnostic, and therapeutic strategies against cancer. Novel more effective and safe adipocytokine-centered therapeutic interventions may pave the way for targeted oncotherapy.

Jemal A, Miller KD, Ma J, Siegel RL, Fedewa SA, Islami F, et al. Higher lung cancer incidence in young women than young men in the United States. N Engl J Med. 2018;378:1999–2009. https://doi.org/10.1056/NEJMoa1715907.CrossRefPubMed

Pischon T, Nimptsch K. Obesity and risk of cancer: an introductory overview. Recent Results Cancer Res. 2016;208:1–15. https://doi.org/10.1007/978-3-319-42542-9_1.CrossRefPubMed

Kelly T, Yang W, Chen C-S, Reynolds K, He J. Global burden of obesity in 2005 and projections to 2030. Int J Obes. 2008;32:1431–7. https://doi.org/10.1038/ijo.2008.102.CrossRef

Ackerman SE, Blackburn OA, Marchildon F, Cohen P. Insights into the link between obesity and cancer. Curr Obes Rep. 2017;6:195–203. https://doi.org/10.1007/s13679-017-0263-x.CrossRefPubMed

Lauby-Secretan B, Scoccianti C, Loomis D, Grosse Y, Bianchini F, Straif K, et al. Body fatness and cancer—viewpoint of the IARC Working Group. N Engl J Med. 2016;375:794–8. https://doi.org/10.1056/NEJMsr1606602.CrossRefPubMed

Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med. 2003;348:1625–38. https://doi.org/10.1056/NEJMoa021423.CrossRefPubMed

Renehan AG, Tyson M, Egger M, Heller RF, Zwahlen M. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet. 2008;371:569–78. https://doi.org/10.1016/S0140-6736(08)60269-X.CrossRef

Britton KA, Massaro JM, Murabito JM, Kreger BE, Hoffmann U, Fox CS. Body fat distribution, incident cardiovascular disease, cancer, and all-cause mortality. J Am Coll Cardiol. 2013;62:921–5. https://doi.org/10.1016/j.jacc.2013.06.027.CrossRefPubMedPubMedCentral

Lichtman MA. Obesity and neoplasms of lymphohematopoietic cells. Blood Adv. 2016;1:101–3. https://doi.org/10.1182/bloodadvances.2016001685.CrossRefPubMedPubMedCentral

10.

Wallin A, Larsson SC. Body mass index and risk of multiple myeloma: a meta-analysis of prospective studies. Eur J Cancer. 2011;47:1606–15. https://doi.org/10.1016/j.ejca.2011.01.020.CrossRefPubMed

11.

Dalamaga M, Christodoulatos GS. Adiponectin as a biomarker linking obesity and adiposopathy to hematologic malignancies. Horm Mol Biol Clin Investig. 2015;23:5–20. https://doi.org/10.1515/hmbci-2015-0016.CrossRefPubMed

12.

Larsson SC, Wolk A. Overweight and obesity and incidence of leukemia: a meta-analysis of cohort studies. Int J Cancer. 2008;122:1418–21. https://doi.org/10.1002/ijc.23176.CrossRefPubMed

13.

Larsson SC, Wolk A. Obesity and risk of non-Hodgkin’s lymphoma: a meta-analysis. Int J Cancer. 2007;121:1564–70. https://doi.org/10.1002/ijc.22762.CrossRefPubMed

14.

Park Y, Colditz GA. Diabetes and adiposity: a heavy load for cancer. Lancet Diabetes Endocrinol. 2018;6:82–3. https://doi.org/10.1016/S2213-8587(17)30396-0.CrossRefPubMed

15.

van Kruijsdijk RCM, van der Wall E, Visseren FLJ. Obesity and cancer: the role of dysfunctional adipose tissue. Cancer Epidemiol Biomark Prev. 2009;18:2569–78. https://doi.org/10.1158/1055-9965.EPI-09-0372.CrossRef

16.

•• Dalamaga M, Christodoulatos GS, Mantzoros CS. The role of extracellular and intracellular nicotinamide phosphoribosyl-transferase in cancer: diagnostic and therapeutic perspectives and challenges. Metabolism. 2018;82:72–87. https://doi.org/10.1016/j.metabol.2018.01.001. This review explores the role of Nampt in cancer pathophysiology as well as synopsizes the mechanisms underlying the association between extracellular and intracellular Nampt and malignancy. CrossRefPubMed

17.

•• Dalamaga M, Diakopoulos KN, Mantzoros CS. The role of adiponectin in cancer: a review of current evidence. Endocr Rev. 2012;33:547–94. https://doi.org/10.1210/er.2011-1015. This review investigates the role of adiponectin in cancer pathophysiology as well as synopsizes the mechanisms underlying the association between adiponectin and cancer. CrossRefPubMedPubMedCentral

18.

Dalamaga M. Obesity, insulin resistance, adipocytokines and breast cancer: new biomarkers and attractive therapeutic targets. World J Exp Med. 2013;3:34–42. https://doi.org/10.5493/wjem.v3.i3.34.CrossRefPubMedPubMedCentral

19.

Pickens CA, Sordillo LM, Zhang C, Fenton JI. Obesity is positively associated with arachidonic acid-derived 5- and 11-hydroxyeicosatetraenoic acid (HETE). Metabolism. 2017;70:177–91. https://doi.org/10.1016/j.metabol.2017.01.034.CrossRefPubMed

20.

Lee MK, Kim J-Y, Kim D-I, Kang D-W, Park J, Ahn K-Y, et al. Effect of home-based exercise intervention on fasting insulin and adipocytokines in colorectal cancer survivors: a randomized controlled trial. Metabolism. 2017;76:23–31. https://doi.org/10.1016/j.metabol.2017.07.005.CrossRefPubMed

21.

Mendonça FM, de Sousa FR, Barbosa AL, Martins SC, Araújo RL, Soares R, et al. Metabolic syndrome and risk of cancer: which link? Metabolism. 2015;64:182–9. https://doi.org/10.1016/j.metabol.2014.10.008.CrossRefPubMed

22.

Cabia B, Andrade S, Carreira MC, Casanueva FF, Crujeiras AB. A role for novel adipose tissue-secreted factors in obesity-related carcinogenesis. Obes Rev. 2016;17:361–76. https://doi.org/10.1111/obr.12377.CrossRefPubMed

23.

Sahin-Efe A, Katsikeris F, Mantzoros CS. Advances in adipokines. Metabolism. 2012;61:1659–65. https://doi.org/10.1016/j.metabol.2012.09.001.CrossRefPubMed

24.

Reizes O, Berger NA. Adipocytokines, energy balance, and cancer. Springer International Publishing Switzerland; 2017. https://doi.org/10.1007/978-3-319-41677-9

25.

Dalamaga M. Resistin as a biomarker linking obesity and inflammation to cancer: potential clinical perspectives. Biomark Med. 2014;8:107–18. https://doi.org/10.2217/bmm.13.99.CrossRefPubMed

26.

Dalamaga M, Chou SH, Shields K, Papageorgiou P, Polyzos SA, Mantzoros CS. Leptin at the intersection of neuroendocrinology and metabolism: current evidence and therapeutic perspectives. Cell Metab. 2013;18:29–42. https://doi.org/10.1016/j.cmet.2013.05.010.CrossRef

27.

Moon H-S, Dalamaga M, Kim S-Y, Polyzos SA, Hamnvik O-P, Magkos F, et al. Leptin’s role in lipodystrophic and nonlipodystrophic insulin-resistant and diabetic individuals. Endocr Rev. 2013;34:377–412. https://doi.org/10.1210/er.2012-1053.CrossRefPubMedPubMedCentral

28.

Lee CH, Woo YC, Wang Y, Yeung CY, Xu A, Lam KSL. Obesity, adipokines and cancer: an update. Clin Endocrinol. 2015;83:147–56. https://doi.org/10.1111/cen.12667.CrossRef

29.

Kadowaki T, Yamauchi T. Adiponectin and adiponectin receptors. Endocr Rev. 2005;26:439–51. https://doi.org/10.1210/er.2005-0005.CrossRefPubMed

30.

Brochu-Gaudreau K, Rehfeldt C, Blouin R, Bordignon V, Murphy BD, Palin M-F. Adiponectin action from head to toe. Endocrine. 2010;37:11–32. https://doi.org/10.1007/s12020-009-9278-8.CrossRefPubMed

31.

Wang Y, Lam KSL, Xu JY, Lu G, Xu LY, Cooper GJS, et al. Adiponectin inhibits cell proliferation by interacting with several growth factors in an oligomerization-dependent manner. J Biol Chem. 2005;280:18341–7. https://doi.org/10.1074/jbc.M501149200.CrossRefPubMed

32.

Ziemke F, Mantzoros CS. Adiponectin in insulin resistance: lessons from translational research. Am J Clin Nutr. 2010;91:258S–61S. https://doi.org/10.3945/ajcn.2009.28449C.CrossRefPubMed

33.

Barb D, Williams CJ, Neuwirth AK, Mantzoros CS. Adiponectin in relation to malignancies: a review of existing basic research and clinical evidence. Am J Clin Nutr. 2007;86:s858–66. https://doi.org/10.1093/ajcn/86.3.858S.CrossRefPubMed

34.

Kelesidis I, Kelesidis T, Mantzoros CS. Adiponectin and cancer: a systematic review. Br J Cancer. 2006;94:1221–5. https://doi.org/10.1038/sj.bjc.6603051.CrossRefPubMedPubMedCentral

35.

Hivert M-F, Sullivan LM, Fox CS, Nathan DM, D’Agostino RB, Wilson PWF, et al. Associations of adiponectin, resistin, and tumor necrosis factor-alpha with insulin resistance. J Clin Endocrinol Metab. 2008;93:3165–72. https://doi.org/10.1210/jc.2008-0425.CrossRefPubMedPubMedCentral

36.

Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE, et al. Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab. 2001;86:1930–5. https://doi.org/10.1210/jcem.86.5.7463.CrossRefPubMed

37.

Hotta K, Funahashi T, Arita Y, Takahashi M, Matsuda M, Okamoto Y, et al. Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol. 2000;20:1595–9.CrossRef

38.

Heidemann C, Sun Q, van Dam RM, Meigs JB, Zhang C, Tworoger SS, et al. Total and high-molecular-weight adiponectin and resistin in relation to the risk for type 2 diabetes in women. Ann Intern Med. 2008;149:307–16.CrossRef

39.

Mazaki-Tovi S, Romero R, Vaisbuch E, Erez O, Mittal P, Chaiworapongsa T, et al. Maternal serum adiponectin multimers in gestational diabetes. J Perinat Med. 2009;37:637–50. https://doi.org/10.1515/JPM.2009.101.CrossRefPubMedPubMedCentral

40.

Trujillo ME, Scherer PE. Adiponectin—journey from an adipocyte secretory protein to biomarker of the metabolic syndrome. J Intern Med. 2005;257:167–75. https://doi.org/10.1111/j.1365-2796.2004.01426.x.CrossRefPubMed

41.

Durante-Mangoni E, Zampino R, Marrone A, Tripodi M-F, Rinaldi L, Restivo L, et al. Hepatic steatosis and insulin resistance are associated with serum imbalance of adiponectin/tumour necrosis factor-alpha in chronic hepatitis C patients. Aliment Pharmacol Ther. 2006;24:1349–57. https://doi.org/10.1111/j.1365-2036.2006.03114.x.CrossRefPubMed

42.

Lee DY, Rhee E-J, Chang Y, Sohn CIL, Shin H-C, Ryu S, et al. Impact of systemic inflammation on the relationship between insulin resistance and all-cause and cancer-related mortality. Metabolism. 2018;81:52–62. https://doi.org/10.1016/j.metabol.2017.11.014.CrossRefPubMed

43.

Delporte ML, Brichard SM, Hermans MP, Beguin C, Lambert M. Hyperadiponectinaemia in anorexia nervosa. Clin Endocrinol. 2003;58:22–9.CrossRef

44.

Ebina K, Fukuhara A, Ando W, Hirao M, Koga T, Oshima K, et al. Serum adiponectin concentrations correlate with severity of rheumatoid arthritis evaluated by extent of joint destruction. Clin Rheumatol. 2009;28:445–51. https://doi.org/10.1007/s10067-008-1074-y.CrossRefPubMed

45.

Senolt L, Pavelka K, Housa D, Haluzík M. Increased adiponectin is negatively linked to the local inflammatory process in patients with rheumatoid arthritis. Cytokine. 2006;35:247–52. https://doi.org/10.1016/j.cyto.2006.09.002.CrossRefPubMed

46.

Zoccali C, Mallamaci F. Adiponectin and leptin in chronic kidney disease: causal factors or mere risk markers? J Ren Nutr. 2011;21:87–91. https://doi.org/10.1053/j.jrn.2010.10.014.CrossRefPubMed

47.

Schulze MB, Shai I, Rimm EB, Li T, Rifai N, Hu FB. Adiponectin and future coronary heart disease events among men with type 2 diabetes. Diabetes. 2005;54:534–9.CrossRef

48.

Mantzoros CS, Li T, Manson JE, Meigs JB, Hu FB. Circulating adiponectin levels are associated with better glycemic control, more favorable lipid profile, and reduced inflammation in women with type 2 diabetes. J Clin Endocrinol Metab. 2005;90:4542–8. https://doi.org/10.1210/jc.2005-0372.CrossRefPubMed

49.

Gorgui J, Gasbarrino K, Georgakis MK, Karalexi MA, Nauche B, Petridou ET, et al. Circulating adiponectin levels in relation to carotid atherosclerotic plaque presence, ischemic stroke risk, and mortality: a systematic review and meta-analyses. Metabolism. 2017;69:51–66. https://doi.org/10.1016/j.metabol.2017.01.002.CrossRefPubMed

50.

Li S, Shin HJ, Ding EL, van Dam RM. Adiponectin levels and risk of type 2 diabetes: a systematic review and meta-analysis. JAMA. 2009;302:179–88. https://doi.org/10.1001/jama.2009.976.CrossRefPubMed

51.

• Boutari C, Mantzoros CS. Inflammation: a key player linking obesity with malignancies. Metabolism. 2018;81:A3–6. https://doi.org/10.1016/j.metabol.2017.12.015. This study reviews the relationship of obesity and cancer under the common theme of inflammation. CrossRefPubMed

52.

Diedrich J, Gusky HC, Podgorski I. Adipose tissue dysfunction and its effects on tumor metabolism. Horm Mol Biol Clin Investig. 2015;21:17–41. https://doi.org/10.1515/hmbci-2014-0045.CrossRefPubMedPubMedCentral

53.

Pérez-Hernández AI, Catalán V, Gómez-Ambrosi J, Rodríguez A, Frühbeck G. Mechanisms linking excess adiposity and carcinogenesis promotion. Front Endocrinol (Lausanne). 2014;5:65. https://doi.org/10.3389/fendo.2014.00065.CrossRef

54.

Wang Y, Lam KSL, Xu A. Adiponectin as a negative regulator in obesity-related mammary carcinogenesis. Cell Res. 2007;17:280–2. https://doi.org/10.1038/cr.2007.14.CrossRefPubMed

55.

Ma J-J, Shang J, Wang H, Sui J-R, Liu K, Du J-X. Serum adiponectin levels are inversely correlated with leukemia: a meta-analysis. J Cancer Res Ther. 2016;12:897–902. https://doi.org/10.4103/0973-1482.186695.CrossRefPubMed

56.

Wei T, Ye P, Peng X, Wu L-L, Yu G-Y. Circulating adiponectin levels in various malignancies: an updated meta-analysis of 107 studies. Oncotarget. 2016;7:48671–91. https://doi.org/10.18632/oncotarget.8932.CrossRefPubMedPubMedCentral

57.

Goktas S, Yilmaz MI, Caglar K, Sonmez A, Kilic S, Bedir S. Prostate cancer and adiponectin. Urology. 2005;65:1168–72. https://doi.org/10.1016/j.urology.2004.12.053.CrossRefPubMed

58.

Gialamas SP, Petridou ET, Tseleni-Balafouta S, Spyridopoulos TN, Matsoukis IL, Kondi-Pafiti A, et al. Serum adiponectin levels and tissue expression of adiponectin receptors are associated with risk, stage, and grade of colorectal cancer. Metabolism. 2011;60:1530–8. https://doi.org/10.1016/j.metabol.2011.03.020.CrossRefPubMed

59.

Petridou E, Mantzoros C, Dessypris N, Koukoulomatis P, Addy C, Voulgaris Z, et al. Plasma adiponectin concentrations in relation to endometrial cancer: a case-control study in Greece. J Clin Endocrinol Metab. 2003;88:993–7. https://doi.org/10.1210/jc.2002-021209.CrossRefPubMed

60.

Mantzoros C, Petridou E, Alexe D-M, Skalkidou A, Dessypris N, Papathoma E, et al. Serum adiponectin concentrations in relation to maternal and perinatal characteristics in newborns. Eur J Endocrinol. 2004;151:741–6.CrossRef

61.

Miyoshi Y, Funahashi T, Kihara S, Taguchi T, Tamaki Y, Matsuzawa Y, et al. Association of serum adiponectin levels with breast cancer risk. Clin Cancer Res. 2003;9:5699–704.PubMed

62.

Chen D-C, Chung Y-F, Yeh Y-T, Chaung H-C, Kuo F-C, Fu O-Y, et al. Serum adiponectin and leptin levels in Taiwanese breast cancer patients. Cancer Lett. 2006;237:109–14. https://doi.org/10.1016/j.canlet.2005.05.047.CrossRefPubMed

63.

Jeong Y-J, Bong J-G, Park S-H, Choi J-H, Oh H-K. Expression of leptin, leptin receptor, adiponectin, and adiponectin receptor in ductal carcinoma in situ and invasive breast cancer. J Breast Cancer. 2011;14:96–103. https://doi.org/10.4048/jbc.2011.14.2.96.CrossRefPubMedPubMedCentral

64.

•• Kim S, Lee Y, Kim JW, Son Y-J, Ma MJ, Um J-H, et al. Discovery of a novel potent peptide agonist to adiponectin receptor 1. PLoS One. 2018;13:e0199256. https://doi.org/10.1371/journal.pone.0199256. This study describes the discovery of an adiponectin agonist peptide that may provide insight in the development of malignancy therapeutics. CrossRefPubMedPubMedCentral

65.

Friedman JM, Halaas JL. Leptin and the regulation of body weight in mammals. Nature. 1998;395:763–70. https://doi.org/10.1038/27376.CrossRef

66.

Mantzoros CS, Magkos F, Brinkoetter M, Sienkiewicz E, Dardeno TA, Kim S-Y, et al. Leptin in human physiology and pathophysiology. Am J Physiol Endocrinol Metab. 2011;301:E567–84. https://doi.org/10.1152/ajpendo.00315.2011.CrossRefPubMedPubMedCentral

67.

Booth A, Magnuson A, Fouts J, Foster M. Adipose tissue, obesity and adipokines: role in cancer promotion. Horm Mol Biol Clin Investig. 2015;21:57–74. https://doi.org/10.1515/hmbci-2014-0037.CrossRefPubMed

68.

Sharma D, Saxena NK, Vertino PM, Anania FA. Leptin promotes the proliferative response and invasiveness in human endometrial cancer cells by activating multiple signal-transduction pathways. Endocr Relat Cancer. 2006;13:629–40. https://doi.org/10.1677/erc.1.01169.CrossRefPubMedPubMedCentral

69.

Choi J-H, Park S-H, Leung PCK, Choi K-C. Expression of leptin receptors and potential effects of leptin on the cell growth and activation of mitogen-activated protein kinases in ovarian cancer cells. J Clin Endocrinol Metab. 2005;90:207–10. https://doi.org/10.1210/jc.2004-0297.CrossRefPubMed

70.

Wang Y, Prywes R. Activation of the c-fos enhancer by the erk MAP kinase pathway through two sequence elements: the c-fos AP-1 and p62TCF sites. Oncogene. 2000;19:1379–85. https://doi.org/10.1038/sj.onc.1203443.CrossRefPubMed

71.

Frankenberry KA, Skinner H, Somasundar P, McFadden DW, Vona-Davis LC. Leptin receptor expression and cell signaling in breast cancer. Int J Oncol. 2006;28:985–93.PubMed

72.

Harris HR, Tworoger SS, Hankinson SE, Rosner BA, Michels KB. Plasma leptin levels and risk of breast cancer in premenopausal women. Cancer Prev Res. 2011;4:1449–56. https://doi.org/10.1158/1940-6207.CAPR-11-0125.CrossRef

73.

Niu J, Jiang L, Guo W, Shao L, Liu Y, Wang L. The association between leptin level and breast cancer: a meta-analysis. PLoS One. 2013;8:e67349. https://doi.org/10.1371/journal.pone.0067349.CrossRefPubMedPubMedCentral

74.

Andò S, Catalano S. The multifactorial role of leptin in driving the breast cancer microenvironment. Nat Rev Endocrinol. 2011;8:263–75. https://doi.org/10.1038/nrendo.2011.184.CrossRefPubMed

75.

García-Robles MJ, Segura-Ortega JE, Fafutis-Morris M. The biology of leptin and its implications in breast cancer: a general view. J Interf Cytokine Res. 2013;33:717–27. https://doi.org/10.1089/jir.2012.0168.CrossRef

76.

Jardé T, Perrier S, Vasson M-P, Caldefie-Chézet F. Molecular mechanisms of leptin and adiponectin in breast cancer. Eur J Cancer. 2011;47:33–43. https://doi.org/10.1016/j.ejca.2010.09.005.CrossRefPubMed

77.

Dubois V, Jardé T, Delort L, Billard H, Bernard-Gallon D, Berger E, et al. Leptin induces a proliferative response in breast cancer cells but not in normal breast cells. Nutr Cancer. 2014;66:645–55. https://doi.org/10.1080/01635581.2014.894104.CrossRefPubMed

78.

Allott EH, Masko EM, Freedland SJ. Obesity and prostate cancer: weighing the evidence. Eur Urol. 2013;63:800–9. https://doi.org/10.1016/j.eururo.2012.11.013.CrossRefPubMed

79.

Dong Z, Fu S, Xu X, Yang Y, Du L, Li W, et al. Leptin-mediated regulation of ICAM-1 is Rho/ROCK dependent and enhances gastric cancer cell migration. Br J Cancer. 2014;110:1801–10. https://doi.org/10.1038/bjc.2014.70.CrossRefPubMedPubMedCentral

80.

Koda M, Sulkowska M, Kanczuga-Koda L, Surmacz E, Sulkowski S. Overexpression of the obesity hormone leptin in human colorectal cancer. J Clin Pathol. 2006;60:902–6. https://doi.org/10.1136/jcp.2006.041004.CrossRef

81.

Dalamaga M, Polyzos SA, Karmaniolas K, Chamberland J, Lekka A, Triantafilli M, et al. Fetuin-A levels and free leptin index are reduced in patients with chronic lymphocytic leukemia: a hospital-based case-control study. Leuk Lymphoma. 2016;57:577–84. https://doi.org/10.3109/10428194.2015.1075523.CrossRefPubMed

82.

Dalamaga M, Karmaniolas K, Panagiotou A, Hsi A, Chamberland J, Dimas C, et al. Low circulating adiponectin and resistin, but not leptin, levels are associated with multiple myeloma risk: a case–control study. Cancer Causes Control. 2009;20:193–9. https://doi.org/10.1007/s10552-008-9233-7.CrossRefPubMed

83.

Pan H, Deng L-L, Cui J-Q, Shi L, Yang Y-C, Luo J-H, et al. Association between serum leptin levels and breast cancer risk. Medicine (Baltimore). 2018;97:e11345. https://doi.org/10.1097/MD.0000000000011345.CrossRef

84.

Wang P-P, He X-Y, Wang R, Wang Z, Wang Y-G. High leptin level is an independent risk factor of endometrial cancer: a meta-analysis. Cell Physiol Biochem. 2014;34:1477–84. https://doi.org/10.1159/000366352.CrossRefPubMed

85.

• Tong X, Ma Y, Zhou Q, He J, Peng B, Liu S, et al. Serum and tissue leptin in lung cancer: a meta-analysis. Oncotarget. 2017;8:19699–711. https://doi.org/10.18632/oncotarget.14963. This meta-analysis investigated the relation of leptin serum and tissue levels with lung cancer. CrossRefPubMedPubMedCentral

86.

Dalamaga M, Migdalis I, Fargnoli JL, Papadavid E, Bloom E, Mitsiades N, et al. Pancreatic cancer expresses adiponectin receptors and is associated with hypoleptinemia and hyperadiponectinemia: a case–control study. Cancer Causes Control. 2009;20:625–33. https://doi.org/10.1007/s10552-008-9273-z.CrossRefPubMed

87.

Dalamaga M, Polyzos SA, Karmaniolas K, Chamberland J, Lekka A, Migdalis I, et al. Circulating fetuin-A in patients with pancreatic cancer: a hospital-based case-control study. Biomarkers. 2014;19:660–6. https://doi.org/10.3109/1354750X.2014.974071.CrossRefPubMed

88.

Dalamaga M, Crotty BH, Fargnoli J, Papadavid E, Lekka A, Triantafilli M, et al. B-cell chronic lymphocytic leukemia risk in association with serum leptin and adiponectin: a case–control study in Greece. Cancer Causes Control. 2010;21:1451–9. https://doi.org/10.1007/s10552-010-9573-y.CrossRefPubMedPubMedCentral

89.

Dalamaga M, Karmaniolas K, Chamberland J, Nikolaidou A, Lekka A, Dionyssiou-Asteriou A, et al. Higher fetuin-A, lower adiponectin and free leptin levels mediate effects of excess body weight on insulin resistance and risk for myelodysplastic syndrome. Metabolism. 2013;62:1830–9. https://doi.org/10.1016/j.metabol.2013.09.007.CrossRefPubMed

90.

Dalamaga M, Karmaniolas K, Nikolaidou A, Chamberland J, Hsi A, Dionyssiou-Asteriou A, et al. Adiponectin and resistin are associated with risk for myelodysplastic syndrome, independently from the insulin-like growth factor-I (IGF-I) system. Eur J Cancer. 2008;44:1744–53. https://doi.org/10.1016/j.ejca.2008.04.015.CrossRefPubMed

91.

Dalamaga M, Nikolaidou A, Karmaniolas K, Hsi A, Chamberland J, Dionyssiou-Asteriou A, et al. Circulating adiponectin and leptin in relation to myelodysplastic syndrome: a case-control study. Oncology. 2007;73:26–32. https://doi.org/10.1159/000120995.CrossRefPubMed

92.

Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, et al. The hormone resistin links obesity to diabetes. Nature. 2001;409:307–12. https://doi.org/10.1038/35053000.CrossRefPubMed

93.

Krecki R, Drozdz J, Szcześniak P, Orszulak-Michalak D, Krzemińska-Pakuła M. Novel atherogenesis markers for identification of patients with a multivessel coronary artery disease. Kardiol Pol. 2008;66:1173-80-2.

94.

Forrest OA, Chopyk DM, Gernez Y, Brown MR, Conrad CK, Moss RB, et al. Resistin is elevated in cystic fibrosis sputum and correlates negatively with lung function. J Cyst Fibros. 2018; https://doi.org/10.1016/j.jcf.2018.05.018.

95.

Gong W-J, Zheng W, Xiao L, Tan L-M, Song J, Li X-P, et al. Circulating resistin levels and obesity-related cancer risk: a meta-analysis. Oncotarget. 2016;7:57694–704. https://doi.org/10.18632/oncotarget.11034.CrossRefPubMedPubMedCentral

96.

Samal B, Sun Y, Stearns G, Xie C, Suggs S, McNiece I. Cloning and characterization of the cDNA encoding a novel human pre-B-cell colony-enhancing factor. Mol Cell Biol. 1994;14:1431–7.CrossRef

97.

Rongvaux A, Shea RJ, Mulks MH, Gigot D, Urbain J, Leo O, et al. Pre-B-cell colony-enhancing factor, whose expression is up-regulated in activated lymphocytes, is a nicotinamide phosphoribosyltransferase, a cytosolic enzyme involved in NAD biosynthesis. Eur J Immunol. 2002;32:3225–34. https://doi.org/10.1002/1521-4141(200211)32:11<3225::AID-IMMU3225>3.0.CO;2-L.CrossRefPubMed

98.

Ming G, Li X, Yin J, Ai Y, Xu D, Ma X, et al. JAZF1 regulates visfatin expression in adipocytes via PPARα and PPARβ/δ signaling. Metabolism. 2014;63:1012–21. https://doi.org/10.1016/j.metabol.2014.05.006.CrossRefPubMed

99.

Zhang LQ, Heruth DP, Ye SQ. Nicotinamide phosphoribosyltransferase in human diseases. J Bioanal Biomed. 2011;3:13–25. https://doi.org/10.4172/1948-593X.1000038.CrossRefPubMed

100.

Duarte-Pereira S, Silva SS, Azevedo L, Castro L, Amorim A, Silva RM. NAMPT and NAPRT1: novel polymorphisms and distribution of variants between normal tissues and tumor samples. Sci Rep. 2014;4:6311. https://doi.org/10.1038/srep06311.CrossRefPubMedPubMedCentral

101.

Olszanecka-Glinianowicz M, Owczarek A, Bożentowicz-Wikarek M, Brzozowska A, Mossakowska M, Zdrojewski T, et al. Relationship between circulating visfatin/NAMPT, nutritional status and insulin resistance in an elderly population—results from the PolSenior substudy. Metabolism. 2014;63:1409–18. https://doi.org/10.1016/j.metabol.2014.07.013.CrossRefPubMed

102.

Galli M, Van Gool F, Rongvaux A, Andris F, Leo O. The nicotinamide phosphoribosyltransferase: a molecular link between metabolism, inflammation, and cancer. Cancer Res. 2010;70:8–11. https://doi.org/10.1158/0008-5472.CAN-09-2465.CrossRefPubMed

103.

Moschen AR, Gerner RR, Tilg H. Pre-B cell colony enhancing factor/NAMPT/visfatin in inflammation and obesity-related disorders. Curr Pharm Des. 2010;16:1913–20.CrossRef

104.

Park H-J, Kim S-R, Kim SS, Wee H-J, Bae M-K, Ryu MH, et al. Visfatin promotes cell and tumor growth by upregulating Notch1 in breast cancer. Oncotarget. 2014;5:5087–99. https://doi.org/10.18632/oncotarget.2086.CrossRefPubMedPubMedCentral

105.

Moschen AR, Kaser A, Enrich B, Mosheimer B, Theurl M, Niederegger H, et al. Visfatin, an adipocytokine with proinflammatory and immunomodulating properties. J Immunol. 2007;178:1748–58.CrossRef

106.

Audrito V, Serra S, Brusa D, Mazzola F, Arruga F, Vaisitti T, et al. Extracellular nicotinamide phosphoribosyltransferase (NAMPT) promotes M2 macrophage polarization in chronic lymphocytic leukemia. Blood. 2015;125:111–23. https://doi.org/10.1182/blood-2014-07-589069.CrossRefPubMed

107.

Reddy PS, Umesh S, Thota B, Tandon A, Pandey P, Hegde AS, et al. PBEF1/NAmPRTase/Visfatin: a potential malignant astrocytoma/glioblastoma serum marker with prognostic value. Cancer Biol Ther. 2008;7:663–8.CrossRef

108.

Goralski KB, McCarthy TC, Hanniman EA, Zabel BA, Butcher EC, Parlee SD, et al. Chemerin, a novel adipokine that regulates adipogenesis and adipocyte metabolism. J Biol Chem. 2007;282:28175–88. https://doi.org/10.1074/jbc.M700793200.CrossRefPubMed

109.

Wittamer V, Franssen J-D, Vulcano M, Mirjolet J-F, Le Poul E, Migeotte I, et al. Specific recruitment of antigen-presenting cells by chemerin, a novel processed ligand from human inflammatory fluids. J Exp Med. 2003;198:977–85. https://doi.org/10.1084/jem.20030382.CrossRefPubMedPubMedCentral

110.

Bozaoglu K, Bolton K, McMillan J, Zimmet P, Jowett J, Collier G, et al. Chemerin is a novel adipokine associated with obesity and metabolic syndrome. Endocrinology. 2007;148:4687–94. https://doi.org/10.1210/en.2007-0175.CrossRefPubMed

111.

Chakaroun R, Raschpichler M, Klöting N, Oberbach A, Flehmig G, Kern M, et al. Effects of weight loss and exercise on chemerin serum concentrations and adipose tissue expression in human obesity. Metabolism. 2012;61:706–14. https://doi.org/10.1016/j.metabol.2011.10.008.CrossRefPubMed

112.

Aronis KN, Sahin-Efe A, Chamberland JP, Spiro A, Vokonas P, Mantzoros CS. Chemerin levels as predictor of acute coronary events: a case–control study nested within the veterans affairs normative aging study. Metabolism. 2014;63:760–6. https://doi.org/10.1016/j.metabol.2014.02.013.CrossRefPubMed

113.

Wang C, Wu WKK, Liu X, To K-F, Chen GG, Yu J, et al. Increased serum chemerin level promotes cellular invasiveness in gastric cancer: a clinical and experimental study. Peptides. 2014;51:131–8. https://doi.org/10.1016/j.peptides.2013.10.009.CrossRefPubMed

114.

Erdogan S, Yilmaz FM, Yazici O, Yozgat A, Sezer S, Ozdemir N, et al. Inflammation and chemerin in colorectal cancer. Tumour Biol. 2016;37:6337–42. https://doi.org/10.1007/s13277-015-4483-y.CrossRefPubMed

115.

Zhang J, Jin H-C, Zhu A-K, Ying R-C, Wei W, Zhang F-J. Prognostic significance of plasma chemerin levels in patients with gastric cancer. Peptides. 2014;61:7–11. https://doi.org/10.1016/j.peptides.2014.08.007.CrossRefPubMed

116.

Kaur J, Adya R, Tan BK, Chen J, Randeva HS. Identification of chemerin receptor (ChemR23) in human endothelial cells: chemerin-induced endothelial angiogenesis. Biochem Biophys Res Commun. 2010;391:1762–8. https://doi.org/10.1016/j.bbrc.2009.12.150.CrossRefPubMed

117.

Tümmler C, Snapkov I, Wickström M, Moens U, Ljungblad L, Maria Elfman LH, et al. Inhibition of chemerin/CMKLR1 axis in neuroblastoma cells reduces clonogenicity and cell viability in vitro and impairs tumor growth in vivo. Oncotarget. 2017;8:95135–51. https://doi.org/10.18632/oncotarget.19619.CrossRefPubMedPubMedCentral

118.

• Lin Y, Yang X, Liu W, Li B, Yin W, Shi Y, et al. Chemerin has a protective role in hepatocellular carcinoma by inhibiting the expression of IL-6 and GM-CSF and MDSC accumulation. Oncogene. 2017;36:3599–608. https://doi.org/10.1038/onc.2016.516. This study displayed the tumor-suppressive effect of chemerin mediated by the inhibition of the tumor microenvironment inflammation. CrossRefPubMed

119.

Yang R-Z, Lee M-J, Hu H, Pray J, Wu H-B, Hansen BC, et al. Identification of omentin as a novel depot-specific adipokine in human adipose tissue: possible role in modulating insulin action. Am J Physiol Endocrinol Metab. 2006;290:E1253–61. https://doi.org/10.1152/ajpendo.00572.2004.CrossRefPubMed

120.

Shibata R, Ouchi N, Takahashi R, Terakura Y, Ohashi K, Ikeda N, et al. Omentin as a novel biomarker of metabolic risk factors. Diabetol Metab Syndr. 2012;4:37. https://doi.org/10.1186/1758-5996-4-37.CrossRefPubMedPubMedCentral

121.

Panagiotou G, Mu L, Na B, Mukamal KJ, Mantzoros CS. Circulating irisin, omentin-1, and lipoprotein subparticles in adults at higher cardiovascular risk. Metabolism. 2014;63:1265–71. https://doi.org/10.1016/j.metabol.2014.06.001.CrossRefPubMedPubMedCentral

122.

Zhang Y-Y, Zhou L-M. Omentin-1, a new adipokine, promotes apoptosis through regulating Sirt1-dependent p53 deacetylation in hepatocellular carcinoma cells. Eur J Pharmacol. 2013;698:137–44. https://doi.org/10.1016/j.ejphar.2012.11.016.CrossRefPubMed

123.

• Kawashima K, Maeda K, Saigo C, Kito Y, Yoshida K, Takeuchi T. Adiponectin and intelectin-1: important adipokine players in obesity-related colorectal carcinogenesis. Int J Mol Sci 2017;18. doi:https://doi.org/10.3390/ijms18040866. This review analyses the complex relation of the tumor suppresive adipokines, adiponectin and intelectin-1 with colorectal cancer. CrossRef

124.

Shen X-D, Zhang L, Che H, Zhang Y-Y, Yang C, Zhou J, et al. Circulating levels of adipocytokine omentin-1 in patients with renal cell cancer. Cytokine. 2016;77:50–5. https://doi.org/10.1016/j.cyto.2015.09.004.CrossRefPubMed

125.

Aleksandrova K, di Giuseppe R, Isermann B, Biemann R, Schulze M, Wittenbecher C, et al. Circulating omentin as a novel biomarker for colorectal cancer risk: data from the EPIC-Potsdam Cohort Study. Cancer Res. 2016;76:3862–71. https://doi.org/10.1158/0008-5472.CAN-15-3464.CrossRefPubMed

126.

Uyeturk U, Alcelik A, Aktas G, Tekce BK. Post-treatment plasma omentin levels in patients with stage III colon carcinoma. J BUON. 2014;19:681–5.PubMed

127.

Karabulut S, Afsar CU, Karabulut M, Alis H, Bozkurt MA, Aydogan F, et al. Clinical significance of serum omentin-1 levels in patients with pancreatic adenocarcinoma. BBA Clin. 2016;6:138–42. https://doi.org/10.1016/j.bbacli.2016.10.002.CrossRefPubMedPubMedCentral

128.

Li D, Mei H, Pu J, Xiang X, Zhao X, Qu H, et al. Intelectin 1 suppresses the growth, invasion and metastasis of neuroblastoma cells through up-regulation of N-myc downstream regulated gene 2. Mol Cancer. 2015;14:47. https://doi.org/10.1186/s12943-015-0320-6.CrossRefPubMedPubMedCentral

129.

Carpéné C, Dray C, Attané C, Valet P, Portillo MP, Churruca I, et al. Expanding role for the apelin/APJ system in physiopathology. J Physiol Biochem. 2007;63:359–73.CrossRef

130.

Boucher J, Masri B, Daviaud D, Gesta S, Guigné C, Mazzucotelli A, et al. Apelin, a newly identified adipokine up-regulated by insulin and obesity. Endocrinology. 2005;146:1764–71. https://doi.org/10.1210/en.2004-1427.CrossRefPubMed

131.

Castan-Laurell I, Dray C, Attané C, Duparc T, Knauf C, Valet P. Apelin, diabetes, and obesity. Endocrine. 2011;40:1–9. https://doi.org/10.1007/s12020-011-9507-9.CrossRefPubMed

132.

Cavallo MG, Sentinelli F, Barchetta I, Costantino C, Incani M, Perra L, et al. Altered glucose homeostasis is associated with increased serum apelin levels in type 2 diabetes mellitus. PLoS One. 2012;7:e51236. https://doi.org/10.1371/journal.pone.0051236.CrossRefPubMedPubMedCentral

133.

Wysocka MB, Pietraszek-Gremplewicz K, Nowak D. The role of apelin in cardiovascular diseases, obesity and cancer. Front Physiol. 2018;9:557. https://doi.org/10.3389/fphys.2018.00557.CrossRefPubMedPubMedCentral

134.

Lacquaniti A, Altavilla G, Picone A, Donato V, Chirico V, Mondello P, et al. Apelin beyond kidney failure and hyponatremia: a useful biomarker for cancer disease progression evaluation. Clin Exp Med. 2015;15:97–105. https://doi.org/10.1007/s10238-014-0272-y.CrossRefPubMed

135.

Noy N, Li L, Abola MV, Berger NA. Is retinol binding protein 4 a link between adiposity and cancer? Horm Mol Biol Clin Investig. 2015;23:39–46. https://doi.org/10.1515/hmbci-2015-0019.CrossRefPubMedPubMedCentral

136.

Kotnik P, Fischer-Posovszky P, Wabitsch M. RBP4: a controversial adipokine. Eur J Endocrinol. 2011;165:703–11. https://doi.org/10.1530/EJE-11-0431.CrossRefPubMed

137.

Yang Q, Graham TE, Mody N, Preitner F, Peroni OD, Zabolotny JM, et al. Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes. Nature. 2005;436:356–62. https://doi.org/10.1038/nature03711.CrossRefPubMed

138.

Cao H. Adipocytokines in obesity and metabolic disease. J Endocrinol. 2014;220:T47–59. https://doi.org/10.1530/JOE-13-0339.CrossRefPubMedPubMedCentral

139.

Wang Y, Wang Y, Zhang Z. Adipokine RBP4 drives ovarian cancer cell migration. J Ovarian Res. 2018;11:29. https://doi.org/10.1186/s13048-018-0397-9.CrossRefPubMedPubMedCentral

140.

Jiao C, Cui L, Ma A, Li N, Si H. Elevated serum levels of retinol-binding protein 4 are associated with breast cancer risk: a case-control study. PLoS One. 2016;11:e0167498. https://doi.org/10.1371/journal.pone.0167498.CrossRefPubMedPubMedCentral

141.

Fei W, Chen L, Chen J, Shi Q, Zhang L, Liu S, et al. RBP4 and THBS2 are serum biomarkers for diagnosis of colorectal cancer. Oncotarget. 2017;8:92254–64. https://doi.org/10.18632/oncotarget.21173.CrossRefPubMedPubMedCentral

142.

Hida K, Wada J, Eguchi J, Zhang H, Baba M, Seida A, et al. Visceral adipose tissue-derived serine protease inhibitor: a unique insulin-sensitizing adipocytokine in obesity. Proc Natl Acad Sci U S A. 2005;102:10610–5. https://doi.org/10.1073/pnas.0504703102.CrossRefPubMedPubMedCentral

143.

Heiker JT. Vaspin (serpinA12) in obesity, insulin resistance, and inflammation. J Pept Sci. 2014;20:299–306. https://doi.org/10.1002/psc.2621.CrossRefPubMed

144.

Wada J. Vaspin: a novel serpin with insulin-sensitizing effects. Expert Opin Investig Drugs. 2008;17:327–33. https://doi.org/10.1517/13543784.17.3.327.CrossRefPubMed

145.

El-Mesallamy HO, Kassem DH, El-Demerdash E, Amin AI. Vaspin and visfatin/Nampt are interesting interrelated adipokines playing a role in the pathogenesis of type 2 diabetes mellitus. Metabolism. 2011;60:63–70. https://doi.org/10.1016/j.metabol.2010.04.008.CrossRefPubMed

146.

Erdogan S, Sezer S, Baser E, Gun-Eryilmaz O, Gungor T, Uysal S, et al. Evaluating vaspin and adiponectin in postmenopausal women with endometrial cancer. Endocr Relat Cancer. 2013;20:669–75. https://doi.org/10.1530/ERC-13-0280.CrossRefPubMed

147.

Fazeli MS, Dashti H, Akbarzadeh S, Assadi M, Aminian A, Keramati MR, et al. Circulating levels of novel adipocytokines in patients with colorectal cancer. Cytokine. 2013;62:81–5. https://doi.org/10.1016/j.cyto.2013.02.012.CrossRefPubMed

148.

Cymbaluk-Płoska A, Chudecka-Głaz A, Jagodzińska A, Pius-Sadowska E, Sompolska-Rzechuła A, Machaliński B, et al. Evaluation of biologically active substances promoting the development of or protecting against endometrial cancer. Onco Targets Ther. 2018;11:1363–72. https://doi.org/10.2147/OTT.S155942.CrossRefPubMedPubMedCentral

149.

Ramanjaneya M, Chen J, Brown JE, Tripathi G, Hallschmid M, Patel S, et al. Identification of nesfatin-1 in human and murine adipose tissue: a novel depot-specific adipokine with increased levels in obesity. Endocrinology. 2010;151:3169–80. https://doi.org/10.1210/en.2009-1358.CrossRefPubMed

150.

Xu L, Wang H, Gong Y, Pang M, Sun X, Guo F, et al. Nesfatin-1 regulates the lateral hypothalamic area melanin-concentrating hormone-responsive gastric distension-sensitive neurons and gastric function via arcuate nucleus innervation. Metabolism. 2017;67:14–25. https://doi.org/10.1016/j.metabol.2016.10.010.CrossRefPubMed

151.

Riva M, Nitert MD, Voss U, Sathanoori R, Lindqvist A, Ling C, et al. Nesfatin-1 stimulates glucagon and insulin secretion and beta cell NUCB2 is reduced in human type 2 diabetic subjects. Cell Tissue Res. 2011;346:393–405. https://doi.org/10.1007/s00441-011-1268-5.CrossRefPubMed

152.

Xu Y, Pang X, Dong M, Wen F, Zhang Y. Nesfatin-1 inhibits ovarian epithelial carcinoma cell proliferation in vitro. Biochem Biophys Res Commun. 2013;440:467–72. https://doi.org/10.1016/j.bbrc.2013.06.001.CrossRefPubMed

153.

Wang L, Ellis MJ, Gomez JA, Eisner W, Fennell W, Howell DN, et al. Mechanisms of the proteinuria induced by Rho GTPases. Kidney Int. 2012;81:1075–85. https://doi.org/10.1038/ki.2011.472.CrossRefPubMedPubMedCentral

154.

Cetinkaya H, Karagöz B, Bilgi O, Ozgün A, Tunçel T, Emirzeoğlu L, et al. Nesfatin-1 in advanced lung cancer patients with weight loss. Regul Pept. 2013;181:1–3. https://doi.org/10.1016/j.regpep.2012.11.005.CrossRefPubMed

155.

Franzén A, Heinegård D. Isolation and characterization of two sialoproteins present only in bone calcified matrix. Biochem J. 1985;232:715–24.CrossRef

156.

Kahles F, Findeisen HM, Bruemmer D. Osteopontin: a novel regulator at the cross roads of inflammation, obesity and diabetes. Mol Metab. 2014;3:384–93. https://doi.org/10.1016/j.molmet.2014.03.004.CrossRefPubMedPubMedCentral

157.

Lai C-F, Seshadri V, Huang K, Shao J-S, Cai J, Vattikuti R, et al. An osteopontin-NADPH oxidase signaling cascade promotes pro-matrix metalloproteinase 9 activation in aortic mesenchymal cells. Circ Res. 2006;98:1479–89. https://doi.org/10.1161/01.RES.0000227550.00426.60.CrossRefPubMed

158.

Rangaswami H, Bulbule A, Kundu GC. Osteopontin: role in cell signaling and cancer progression. Trends Cell Biol. 2006;16:79–87. https://doi.org/10.1016/j.tcb.2005.12.005.CrossRefPubMed

159.

Johnston NIF, Gunasekharan VK, Ravindranath A, O’Connell C, Johnston PG, El-Tanani MK. Osteopontin as a target for cancer therapy. Front Biosci. 2008;13:4361–72.CrossRef

160.

Rodrigues LR, Teixeira JA, Schmitt FL, Paulsson M, Lindmark-Mänsson H. The role of osteopontin in tumor progression and metastasis in breast cancer. Cancer Epidemiol Biomark Prev. 2007;16:1087–97. https://doi.org/10.1158/1055-9965.EPI-06-1008.CrossRef

161.

Bandopadhyay M, Bulbule A, Butti R, Chakraborty G, Ghorpade P, Ghosh P, et al. Osteopontin as a therapeutic target for cancer. Expert Opin Ther Targets. 2014;18:883–95. https://doi.org/10.1517/14728222.2014.925447.CrossRefPubMed

162.

Rittling SR, Chambers AF. Role of osteopontin in tumour progression. Br J Cancer. 2004;90:1877–81. https://doi.org/10.1038/sj.bjc.6601839.CrossRefPubMedPubMedCentral

163.

Zarling JM, Shoyab M, Marquardt H, Hanson MB, Lioubin MN, Todaro GJ. Oncostatin M: a growth regulator produced by differentiated histiocytic lymphoma cells. Proc Natl Acad Sci U S A. 1986;83:9739–43.CrossRef

164.

Sanchez-Infantes D, White UA, Elks CM, Morrison RF, Gimble JM, Considine RV, et al. Oncostatin m is produced in adipose tissue and is regulated in conditions of obesity and type 2 diabetes. J Clin Endocrinol Metab. 2014;99:E217–25. https://doi.org/10.1210/jc.2013-3555.CrossRefPubMed

165.

Richards CD. The enigmatic cytokine oncostatin M and roles in disease. ISRN Inflamm. 2013;2013:1–23. https://doi.org/10.1155/2013/512103.CrossRef

166.

Miles SA, Martínez-Maza O, Rezai A, Magpantay L, Kishimoto T, Nakamura S, et al. Oncostatin M as a potent mitogen for AIDS-Kaposi’s sarcoma-derived cells. Science. 1992;255:1432–4.CrossRef

167.

Amaral MC, Miles S, Kumar G, Nel AE. Oncostatin-M stimulates tyrosine protein phosphorylation in parallel with the activation of p42MAPK/ERK-2 in Kaposi’s cells. Evidence that this pathway is important in Kaposi cell growth. J Clin Invest. 1993;92:848–57. https://doi.org/10.1172/JCI116659.CrossRefPubMedPubMedCentral

168.

Lapeire L, Hendrix A, Lambein K, Van Bockstal M, Braems G, Van Den Broecke R, et al. Cancer-associated adipose tissue promotes breast cancer progression by paracrine oncostatin M and Jak/STAT3 signaling. Cancer Res. 2014;74:6806–19. https://doi.org/10.1158/0008-5472.CAN-14-0160.CrossRefPubMed

169.

Fossey SL, Bear MD, Kisseberth WC, Pennell M, London CA. Oncostatin M promotes STAT3 activation, VEGF production, and invasion in osteosarcoma cell lines. BMC Cancer. 2011;11:125. https://doi.org/10.1186/1471-2407-11-125.CrossRefPubMedPubMedCentral

170.

Weiss TW, Simak R, Kaun C, Rega G, Pflüger H, Maurer G, et al. Oncostatin M and IL-6 induce u-PA and VEGF in prostate cancer cells and correlate in vivo. Anticancer Res. 2011;31:3273–8.PubMed

171.

• Tawara K, Bolin C, Koncinsky J, Kadaba S, Covert H, Sutherland C, et al. OSM potentiates preintravasation events, increases CTC counts, and promotes breast cancer metastasis to the lung. Breast Cancer Res. 2018;20:–53. https://doi.org/10.1186/s13058-018-0971-5. This study describes the ability of oncostatin-M to facilitate metastasis of breast cancer.

172.

West NR, Murphy LC, Watson PH. Oncostatin M suppresses oestrogen receptor- expression and is associated with poor outcome in human breast cancer. Endocr Relat Cancer. 2012;19:181–95. https://doi.org/10.1530/ERC-11-0326.CrossRefPubMed

173.

Vucenik I, Stains JP. Obesity and cancer risk: evidence, mechanisms, and recommendations. Ann N Y Acad Sci. 2012;1271:37–43. https://doi.org/10.1111/j.1749-6632.2012.06750.x.CrossRefPubMedPubMedCentral

174.

Ligibel JA, Alfano CM, Courneya KS, Demark-Wahnefried W, Burger RA, Chlebowski RT, et al. American Society of Clinical Oncology position statement on obesity and cancer. J Clin Oncol. 2014;32:3568–74. https://doi.org/10.1200/JCO.2014.58.4680.CrossRefPubMedPubMedCentral

175.

Moschen AR, Molnar C, Wolf AM, Weiss H, Graziadei I, Kaser S, et al. Effects of weight loss induced by bariatric surgery on hepatic adipocytokine expression. J Hepatol. 2009;51:765–77. https://doi.org/10.1016/j.jhep.2009.06.016.CrossRefPubMed

176.

Venojärvi M, Wasenius N, Manderoos S, Heinonen OJ, Hernelahti M, Lindholm H, et al. Nordic walking decreased circulating chemerin and leptin concentrations in middle-aged men with impaired glucose regulation. Ann Med. 2013;45:162–70. https://doi.org/10.3109/07853890.2012.727020.CrossRefPubMed

177.

Tee MC, Cao Y, Warnock GL, Hu FB, Chavarro JE. Effect of bariatric surgery on oncologic outcomes: a systematic review and meta-analysis. Surg Endosc. 2013;27:4449–56. https://doi.org/10.1007/s00464-013-3127-9.CrossRefPubMedPubMedCentral

178.

Ashrafian H, Ahmed K, Rowland SP, Patel VM, Gooderham NJ, Holmes E, et al. Metabolic surgery and cancer: protective effects of bariatric procedures. Cancer. 2011;117:1788–99. https://doi.org/10.1002/cncr.25738.CrossRefPubMed

179.

Haider DG, Schindler K, Schaller G, Prager G, Wolzt M, Ludvik B. Increased plasma visfatin concentrations in morbidly obese subjects are reduced after gastric banding. J Clin Endocrinol Metab. 2006;91:1578–81. https://doi.org/10.1210/jc.2005-2248.CrossRefPubMed

180.

Terra X, Auguet T, Guiu-Jurado E, Berlanga A, Orellana-Gavaldà JM, Hernández M, et al. Long-term changes in leptin, chemerin and ghrelin levels following different bariatric surgery procedures: Roux-en-Y gastric bypass and sleeve gastrectomy. Obes Surg. 2013;23:1790–8. https://doi.org/10.1007/s11695-013-1033-9.CrossRefPubMed

181.

Zhu J, Schott M, Liu R, Liu C, Shen B, Wang Q, et al. Intensive glycemic control lowers plasma visfatin levels in patients with type 2 diabetes. Horm Metab Res. 2008;40:801–5. https://doi.org/10.1055/s-0028-1082040.CrossRefPubMed

182.

Mallik R, Chowdhury TA. Metformin in cancer. Diabetes Res Clin Pract. 2018; https://doi.org/10.1016/j.diabres.2018.05.023.CrossRef

183.

Hajavi J, Momtazi AA, Johnston TP, Banach M, Majeed M, Sahebkar A. Curcumin: a naturally occurring modulator of adipokines in diabetes. J Cell Biochem. 2017;118:4170–82. https://doi.org/10.1002/jcb.26121.CrossRefPubMed

184.

Rene Gonzalez R, Watters A, Xu Y, Singh UP, Mann DR, Rueda BR, et al. Leptin-signaling inhibition results in efficient anti-tumor activity in estrogen receptor positive or negative breast cancer. Breast Cancer Res. 2009;11:R36. https://doi.org/10.1186/bcr2321.CrossRefPubMedPubMedCentral

185.

Lanier V, Gillespie C, Leffers M, Daley-Brown D, Milner J, Lipsey C, et al. Leptin-induced transphosphorylation of vascular endothelial growth factor receptor increases Notch and stimulates endothelial cell angiogenic transformation. Int J Biochem Cell Biol. 2016;79:139–50. https://doi.org/10.1016/j.biocel.2016.08.023.CrossRefPubMedPubMedCentral

186.

Khan S, Shukla S, Sinha S, Meeran SM. Role of adipokines and cytokines in obesity-associated breast cancer: therapeutic targets. Cytokine Growth Factor Rev. 2013;24:503–13. https://doi.org/10.1016/j.cytogfr.2013.10.001.CrossRefPubMed

187.

Otvos L, Kovalszky I, Olah J, Coroniti R, Knappe D, Nollmann FI, et al. Optimization of adiponectin-derived peptides for inhibition of cancer cell growth and signaling. Biopolymers. 2015;104:156–66. https://doi.org/10.1002/bip.22627.CrossRefPubMed

188.

Tworoger SS, Eliassen AH, Kelesidis T, Colditz GA, Willett WC, Mantzoros CS, et al. Plasma adiponectin concentrations and risk of incident breast cancer. J Clin Endocrinol Metab. 2007;92:1510–6. https://doi.org/10.1210/jc.2006-1975.CrossRefPubMed

189.

Chong DQ, Mehta RS, Song M, Kedrin D, Meyerhardt JA, Ng K, et al. Prediagnostic plasma adiponectin and survival among patients with colorectal cancer. Cancer Prev Res (Phila). 2015;8:1138–45. https://doi.org/10.1158/1940-6207.CAPR-15-0175.CrossRef

190.

Dalamaga M, Sotiropoulos G, Karmaniolas K, Pelekanos N, Papadavid E, Lekka A. Serum resistin: a biomarker of breast cancer in postmenopausal women? Association with clinicopathological characteristics, tumor markers, inflammatory and metabolic parameters. Clin Biochem. 2013;46:584–90. https://doi.org/10.1016/j.clinbiochem.2013.01.001.CrossRefPubMed

191.

Dalamaga M, Archondakis S, Sotiropoulos G, Karmaniolas K, Pelekanos N, Papadavid E, et al. Could serum visfatin be a potential biomarker for postmenopausal breast cancer? Maturitas. 2012;71:301–8. https://doi.org/10.1016/j.maturitas.2011.12.013.CrossRefPubMed

192.

Zhang K, Zhou B, Zhang P, Zhang Z, Chen P, Pu Y, et al. Genetic variants in NAMPT predict bladder cancer risk and prognosis in individuals from southwest Chinese Han group. Tumour Biol. 2014;35:4031–40. https://doi.org/10.1007/s13277-013-1527-z.CrossRefPubMed

193.

Kalia M. Biomarkers for personalized oncology: recent advances and future challenges. Metabolism. 2015;64:S16–21. https://doi.org/10.1016/j.metabol.2014.10.027.CrossRefPubMed

194.

Burgess S, Timpson NJ, Ebrahim S, Davey Smith G. Mendelian randomization: where are we now and where are we going? Int J Epidemiol. 2015;44:379–88. https://doi.org/10.1093/ije/dyv108.CrossRefPubMed

195.

Ebrahim S, Davey SG. Mendelian randomization: can genetic epidemiology help redress the failures of observational epidemiology? Hum Genet. 2008;123:15–33. https://doi.org/10.1007/s00439-007-0448-6.CrossRefPubMed

196.

Nimptsch K, Song M, Aleksandrova K, Katsoulis M, Freisling H, Jenab M, et al. Genetic variation in the ADIPOQ gene, adiponectin concentrations and risk of colorectal cancer: a Mendelian randomization analysis using data from three large cohort studies. Eur J Epidemiol. 2017;32:419–30. https://doi.org/10.1007/s10654-017-0262-y.CrossRefPubMedPubMedCentral

Title: Classic and Novel Adipocytokines at the Intersection of Obesity and Cancer: Diagnostic and Therapeutic Strategies
Authors: Nikolaos Spyrou
Konstantinos I. Avgerinos
Christos S. Mantzoros
Maria Dalamaga
Publication date: 01-12-2018
Publisher: Springer US
Published in: Current Obesity Reports / Issue 4/2018
Electronic ISSN: 2162-4968
DOI: https://doi.org/10.1007/s13679-018-0318-7

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits

STEP AAG HeroTeaserCollection image/© Tarek / Generated with AI / Stock.adobe.com, ACC 2024 Pediatric and Congenital Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Pulmonary Vascular Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Valvular Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 HF and Cardiomyopathies: Year in Review/© 2024 American College of Cardiology, Woman out walking/© Seventyfour / stock.adobe.com (symbolic image with model), Woman checking smartwatch /© saltdium / stock.adobe.com (symbolic image with model), Cardiac catheterization/© Damian / stock.adobe.com

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose of Review

Recent Findings

Summary

Please log in to get access to this content

Other articles of this Issue 4/2018

Prevalence of Overweight and Obesity in Bangladesh: a Systematic Review of the Literature

Risk Factors and Implications of Childhood Obesity

Epidemiology of Obesity in Adults: Latest Trends

Bipolar Disorder and Obesity: Contributing Factors, Impact on Clinical Course, and the Role of Bariatric Surgery

Towards an Individualized Nutrition Treatment: Role of the Gastrointestinal Microbiome in the Interplay Between Diet and Obesity

Obesity and Sexual Functioning

Highlights from the ACC 2024 Congress

ACC 2024 Congress Coverage