Leptin as a potential therapeutic target for breast cancer prevention and treatment

Expert Opinion on Therapeutic Targets

Volumn 14, Issue 4, 2010, Pages 443-451

  Ray, Amitbha ^a   Cleary, Margot P ^a  

^a UNIVERSITY OF MINNESOTA   (United States)

Author keywords

Adiponectin; Agonists; Antagonists; Breast; Cancer; Leptin

Indexed keywords

ADIPONECTIN; BETA 3 ADRENERGIC RECEPTOR STIMULATING AGENT; LEPTIN; PIOGLITAZONE; ROSIGLITAZONE;

ANTINEOPLASTIC ACTIVITY; BLOOD LEVEL; BREAST TUMOR; CARCINOGENESIS; FOOD INTAKE; HUMAN; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OBESITY; REVIEW;

ANIMALS; ANTINEOPLASTIC AGENTS; BREAST NEOPLASMS; CELL LINE, TUMOR; FEMALE; HUMANS; LEPTIN; MAMMARY NEOPLASMS, EXPERIMENTAL; OBESITY;

EID: 77949566512     PISSN: 14728222     EISSN: None     Source Type: Journal    
DOI: 10.1517/14728221003716466     Document Type: Review

References (106)

1. Kamangar F, Dores GM, Anderson WF. Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol 2006;24:2137-2150
2. Reeves GK, Pirie K, Beral V, et al. Cancer incidence and mortality in relation to body mass index in the Million Women Study: cohort study. Br Med J 2008;100:1-11
3. Santen RJ, Boyd NF, Chlebowski RT, et al. Critical assessment of new risk factors for breast cancer: considerations for development of an improved risk prediction model. Endocr Relat Cancer 2007;14:169-187
4. Carmichael AR. Obesity as a risk factor for development and poor prognosis of breast cancer. BJOG 2006;113:1160-1166
5. Endogenous Hormones and Breast Cancer Collaborative Group. Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women. J Natl Cancer Inst 2003;95:1218-1226
6. Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 2004;89:2548-2556
7. Purohit A, Reed MJ. Regulation of estrogen synthesis in postmenopausal women. Steroids 2002;67:979-983
8. Vona-Davis L, Rose DP. Adipokines as endocrine, paracrine, and autocrine factors in breast cancer risk and progression. Endocr Relat Cancer 2007;14:189-206
9. Pischon T, Nothlilngs U, Boeing H. Obesity and cancer. Proc Nutr Soc 2008;67:128-145
10. Zhang Y, Proenca R, Maffei M, et al. Positional cloning of the mouse obese gene and its human homologue. Nature 1994;372:425-432
11. Giese K, Fantl WJ, Vitt C, et al. Reduction of food intake and weight gain by the ob protein requires a specific secondary structure and is reversible. Mol Med 1996;2:50-58
12. Weigle DS, Bukowski TR, Foster DC, et al. Recombintant ob protein reduces feeding and body weight in the ob/ob mouse. J Clin Invest 1995;96:2065-2070
13. Campfield LA, Smith FJ, Guisez Y, et al. Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural network. Science 1995;269:546-549
14. Hegyi K, Fulop K, Kovacs K, et al. Leptin-induced signal transduction pathways. Cell Biol Int 2004;28:159-169
15. Friedman JM, Halaas JL. Leptin and the regulation of body weight in mammals. Nature 1998;395:763-770
16. Wauters M, Considine RV, Van Gaal L. Human leptin: from an adipocyte hormone to an endorcrine mediator. Eur J Endocrinol 2000;143:293-311
17. Casabiell X, Piñeiro V, Vega F, et al. Leptin, reproduction and sex steroids. Pituitary 2001;4:93-99
18. Fietta P. Focus on leptin, a pleiotropic hormone. Minerva Med 2005;96:65-75
19. Phrakonkham P, Viengchareum S, Belloir C, et al. Dietary xenoestrogens differentially impair 3T3-L1 preadipocytes differentiation and persistently affect leptin synthesis. J Steroid Biochem Mol Biol 2008;110:95-103
20. Simons PJ, van den Pangaart PS, van Roomen CPAA, et al. Cytokine modulation of leptin and adiponectin secretion during in vitro adipogenesis: evidence that tumor necrosis factor-alpha- and interleukin-1betatreated human preadipocytes are potent leptin producers. Cytokine 2005;32:94-103
21. Smith-Kirwin SM, O'Connor DM, Johnston J, et al. Leptin expression in human mammary epithelial cells and breast milk. J Clin Endocrinol Metab 1998;83:1810-1813
22. Ostlund RE Jr, Yang JW, Klein S, Gingerich R. Relation between plasma leptin concentration and body fat, gender, diet, age, and metabolic covariates. J Clin Endocrinol Metab 1996;81:3909-3913
23. Havel PJ, Kasim-Karakas S, Mueller W, et al. Effects of dietary fat content and sustained weight loss. J Clin Endocrinol Metab 1996;81:4406-4413
24. Ahren B. Plasma leptin and insulin in C57Bl/6J mice on a high-fat diet: relation to subsequent changes in body weight. Acta Physiol Scand 1999;165:233-240
25. Yukawa M, Phelan EA, Callahan HS, et al. Leptin levels recover normally in healthy older adults after acute diet-induced weight loss. J Nutr Health Aging 2008;12:652-656
26. Fenton JI, Nunez NP, Yakar S, et al. Diet-induced adiposity alters the serum profile of inflammation in C57BL/6N mice as measured by antibody array. Diabetes Obes Metab 2009;11:343-354
27. Kayemba-Kay's S, Geary MP, Pringle J, et al. Gender, smoking during pregnancy and gestational age influence cord leptin concentrations in newborn infants. Eur J Endocrinol 2008;159:217-224
28. Petridou E, Mantzoros CS, Belechri M, et al. Neonatal leptin levels are strongly associated with female gender, birth length, IGF-I levels and formula feeding. Clin Endocrinol 2005;62:366-371
29. Janecková R. The role of leptin in human physiology and pathophysiology. Physiol Res 2001;50:443-459
30. Tartaglia LA, Dembski M, Weng XD, et al. Identification and expression of leptin receptor, OB-R. Cell 1995;83:1263-1271
31. Bjørbaek C, Uotani S, da Silva B, Flier JS. Divergent signaling capacities of the long and short isoforms of the leptin receptor. J Biol Chem 1997;272:32686-32695
32. Yamashita T, Murakami T, Otani S, et al. Leptin receptor signal transduction: OBRa and OBRb of fa type. Biochem Biophys Res Commun 1998;246:752-759
33. Hileman SM, Tornøe J, Flier JS, Bjørbaek C. Transcellular transport of leptin by the short leptin receptor isoform ObRa in Madin- Darby canine kidney cells. Endocrinology 2000;141:1955-1961
34. Myers MG Jr. Leptin receptor signaling and the regulation of mammalian physiology. Recent Prog Horm Res 2004; 59:287-304
35. Tsuchiya T, Shimizu H, Horie T, Mori M. Expression of leptin receptor in lung: leptin as a growth factor. Eur J Pharm 1999;365:273-279
36. Nakao T, Hino M, Yamane T, et al. Expression of leptin receptor in human leukaemic blast cells. Br J Haemtol 1998;102:740-745
37. Morash B, Johnstone J, Leopold C, et al. The regulation of leptin gene expression in the C6 glioblastoma cell line. Mol Cell Endocrinol 2000;165:97-105
38. Hu X, Juneja SC, Maihle NJ, Cleary MP. Leptin- a growth factor for normal and malignant breast cells and normal mammary gland development. J Natl Cancer Inst 2002;94:1704-1711
39. Laud K, Gourdou I, Pessemesse L, et al. Identification of leptin receptors in human breast cancer: functional activity in the T47-D breast cancer cell line. Mol Cell Endocrinol 2002;188:219-226
40. Dieudonne M-N, Machinal-Quelin F, Serazin-Leroy V, et al. Leptin mediates a proliferative response in human MCF7 breast cancer cells. Biochem Biophys Res Comm 2002;293:622-628
41. Garofalo C, Sisci D, Surmacz E. Leptin interferes with the effects of the antiestrogen ICI 182.780 in MCF-7 breast cancer cell lines. Clin Cancer Res 2004;10:6466-6475
42. Ray A, Nkhata KJ, Cleary MP. Effects of leptin on human breast cancer cell lines in relationship to estrogen receptor and HER2 status. Int J Oncol 2007;30:1499-1509
43. Catalano S, Marsico S, Giordano C, et al. Leptin enhances, via AP-1, expression of aromatase in the MCF-7 cell line. J Biol Chem 2003;278:28668-28676
44. Yin N, Wang D, Zhang H, et al. Molecular mechanisms involved in the growth stimulation of breast cancer cells by leptin. Cancer Res 2004;64:5870-5875
45. Frankenberry KA, Skinner H, Somasundar P, et al. Leptin receptor expression and cell signaling in breast cancer. Int J Oncol 2006;28:985-993
46. Perera CN, Chin HG, Duru N, Camarillo IG. Leptin-regulated gene expression in MCF-7 breast cancer cells: mechanistic insights into leptinregulated mammary tumor growth and progression. J Endocrinol 2008;199:221-233
47. McMurtry V, Simeone A-M, Nieves-Alicea R, Tari AM. Leptin utilizes jun N-terminal kinases to stimulate the invasion of MCF-7 breast cancer cells. Clin Exp Metastasis 2009;26:197-204
48. Chen C, Chang Y-C, Liu C-L, et al. Leptin-induced growth of human ZR- 75-1 breast cancer cells is associated with up-regulation of cyclin D1 and c- Myc and down-regulation of suppor suppressor p53 and p21WAF1/CIP1. Breast Cancer Res Treat 2006;98:121-132
49. Okumura M, Yamamoto M, Sakuma H. Leptin and high glucose stimulate cell proliferation in MCF-7 human breast cancer cells: reciprocal involvement of PKC-alpha and PPAR expression. Biochim Biophys Acta 2002;1592:107-116
50. Gonzalez RR, Cherfils S, Escobar MY, et al. Leptin signaling promotes the growth of mammary tumors and increases the expression of vascular endothelial growth factor (VEGF) and its receptor type two (VEGF-R2). J Biol Chem 2006;281:26320-26328
51. Cleary MP, Ray A, Rogozina OP, et al. Targeting the adiponectin--leptin ratio for prevention of postmenopausal breast cancer. Front Biosci 2009;1:329-357
52. Chen D-C, Chung Y-F, Yeh Y-T, et al. Serum adiponectin and leptin levels in Taiwanese breast cancer patients. Cancer Lett 2006;237:109-114
53. Grossmann ME, Ray A, Dogan S, et al. Balance of adiponectin and leptin in relationship to breast cancer cell growth. Cell Res 2008;18:1154-1156
54. Nkhata KJ, Ray A, Schuster TF, et al. Effects of adiponectin and leptin cotreatment on human breast cancer cell growth. Oncol Rep 2009;21:1611-1619
55. Ishikawa M, Kitayama J, Nagawa H. Enhanced expression of leptin and leptin receptor (OB-R) in human breast cancer. Clin Cancer Res 2004;10:4325-4331
56. Miyoshi Y, Funahashi T, Tanaka S, et al. High expression of leptin receptor mRNA in breast cancer tissue predicts poor prognosis for patients with high, not low serum leptin levels. Int J Cancer 2006;118:1414-1419
57. Révillion F, Charlier M, Lhotellier V, et al. Messenger RNA expression of leptin and leptin receptors and their prognostic value in 322 primary breast cancers. Clin Cancer Res 2006;12:2088-2094
58. Jardé T, Caldefie-Chézet F, Damez M, et al. Leptin and leptin receptor involvement in cancer development: a study on primary breast carcinoma. Oncol Rep 2008;19:905-911
59. Suzuki R, Rylander-Rudqvist T, Ye W, et al. Body weight and postmenopausal breast cancer risk defined by estrogen and progesterone receptor status among Swedish women: a prospective study. Int J Cancer 2006;119:1683-1689
60. Setiawan VW, Monroe KR, Wilkens LR, et al. Breast cancer risk factor defined by estrogen and progesterone receptor status. The Multiethnic Cohort Study. Am J Epidemiol 2009;169:1251-1259
61. Cleary MP, Phillips FC, Getzin SC, et al. Genetically obese MMTV-TGF-alpha/LepobLepob mice do not develop of mammary tumors. Breast Cancer Res Treat 2003;77:205-215
62. Cleary MP, Juneja SC, Phillips FC, et al. Leptin receptor deficient MMTV-TGF-alpha/ LeprdbLeprdb female mice do not develop oncogene-induced mammary tumors. Exp Biol Med 2004;229:182-193
63. Cleary MP, Grande JP, Maihle NJ. Effect of a high fat diet on body weight and mammary tumor latency in MMTV-TGF-alpha mice. Int J Obesity 2004;28:956-962
64. Dogan S, Hu X, Zhang Y, et al. Effects of high fat diet and/or body weight on mammary tumor leptin and apoptosis signaling pathways in MMTV-TGF-alpha mice. Breast Cancer Res 2007;9:R91
65. Cleary MP, Grande JP, Juneja SC, Maihle NJ. Effect of dietary-induced obesity and mammary tumor development in MMTV-neu female mice. Nutr Cancer 2004;50:174-180
66. Lee WM, Lu S, Medline A, Archer MC. Susceptibility of lean and obese Zucker rats to tumorigenesis induced by Nmethyl- N-nitrosurea. Cancer Lett 2001;162:155-160
67. Hakkak R, Holley AW, MacLeod SL, et al. Obesity promotes 7,12-dimethylbenz(a)anthracene-induced mammary tumor development in female zucker rats. Breast Cancer Res 2005;7:R627-33
68. Cleary MP, Hu X, Grossmann ME, et al. Prevention of mammary tumorigenesis by intermittent caloric restriction, does caloric intake during refeeding modulate the response? Exp Biol Med 2007;232:70-80
69. Gonzalez RR, Watters A, Xu Y, 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
70. Gonzalez RR, Leavis PC. A peptide derived from the human leptin molecule is a potent inhibitor of the leptin receptor function in rabbit endometrial cells. Endocrine 2003;21:185-195
71. Salomon G, Niv-Spector L, Gussakovsky EE, Gertler A. Large-scale preparation of biologically active mouse and rat leptins and their L39A/D40A/ F1A muteins which act as potent antagonists. Protein Expr Purif 2006;47:128-136
72. Peelman F, Van Beneden K, Zabeau L, et al. Mapping of the leptin binding sites and design of a leptin antagonist. J Biol Chem 2004;279:41038-41046
73. Niv-Spector L, Gonen-Berger D, Gourdou I, et al. Identification of the hydrophobic strand in the A-B loop of leptin as major binding site III: implications for large-scale preparation of potent recombinant human and ovine leptin antagonists. Biochem J 2005;391:221-230
74. Solomon G, Niv-Spector L, Gonen- Berger D, et al. Preparation of leptin antagonists by site-directed mutagenesis of human, ovine, rat, and mouse leptin's site III. Implications on blocking undesired leptin action in vivo. Ann NY Acad Sci 2006;1091:531-539
75. Peters JH, Simasko SM, Ritter RC. Leptin analog antagonizes leptin effects on food intake and body weight but mimics leptin-induced vagal afferent activation. Endocrinology 2007;148:2878-2885
76. Grasso P, White DW, Tartaglia LA, et al. Inhibitory effects of leptin-related synthetic peptide 116-130 on food intake and body weight gain in female C57BL/6J ob/ob mice may not be mediated by peptide activation of the long isoform of the leptin receptor. Diabetes 1999;48:2204-2209
77. Rozhavskaya-Arena M, Lee DW, Leinung MC, Grasso P. Design of a synthetic leptin agonist: effects on energy balance, glucose homeostasis, and thermoregulation. Endocrinology 2000;141:2501-2507
78. Zhang J, Matheny MK, Tümer N, et al. Leptin antagonist reveals that the normalization of caloric intake and the thermic effect of food after high-fat feeding are leptin dependent. Am J Physiol 2007;292:868-874
79. Fazeli M, Zarkesh-Estahani H, Wu Z, et al. Identification of a monoclonal antibody against the leptin receptor that acts as an antagonist and blocks human monocyte and T cell activation. J Immunol Methods 2006;312:190-200
80. Gertler A. Development of leptin antagonists and their potential use in experimental biology and medicine. Trends Endocrinol Metab 2006;17:372-378
81. Otvos L Jr, Terrasi M, Cascio S, et al. Development of pharmacologically improved peptide agonist of the leptin receptor. Biochim Biophys Acta 2008;1783:1745-1754
82. Omachi A, Ishioka K, Uozumi A. beta3-Adrenoreceptor agonist AJ-9677 reduces body fat in obese beagles. Res Vet Sci 2007;83:5-11
83. Grossmann ME, Nkhata KJ, Mizuno NK, et al. Effects of adiponectin on breast cancer cell growth and signaling. Br J Cancer 2008;98:370-378
84. Dos Santos E, Benaitreau D, Dieudonne M-NL, et al. Adiponectin mediates an antiproliferative response in human MDA-MB-231 breast cancer cells. Oncol Rep 2008;20:971-988
85. Jardé T, Caldefie-Chéet F, Goncalves-Mendes N, et al. Involvement of adiponectin and leptin in breast cancer: clinical and in vitro studies. Endocr Relat Cancer 2009;16(4):1197-1210
86. Nkhata KJ, Ray A, Dogan S, et al. Mammary tumor development from T47D human breast cancer cells in obese ovariectomized mice with and without estradiol supplements. Breast Cancer Res Treat 2009;114:71-83
87. Dogan S, Rogozina OP, Loshkin A, et al. Comparison of chronic vs intermittent calorie restriction on mammary tumor incidence and serum adiponecin and leptin levels in MMTV-TGF-alpha mice at different ages. Oncol Lett 2010;1:167-176
88. Bullen JW Jr, Bluher S, Kelesidis T, Mantzoros C. Regulation of adiponectin and its receptors in response to development of diet-induced obesity in mice. Am J Physiol 2007;292:E1079-86
89. Varady KA, Allister CA, Roohk DJ, Hellerstein MK. Improvements in body fat distribution and criculating adiponectin by alternate-day fasting versus caloric restriction. J Nutr Biochem 2009;21:188-195
90. Flachs P, Mohamed-Ali V, Horakova O, et al. Polyunsaturated fatty acids of marine origin induce adiponectin in mice fed a high-fat diet. Diabetologia 2006;49:394-397
91. Ramel A, Parra D, Martinéz JA, et al. Effects of seafood consumption and weight loss on fasting leptin and ghrelin concentrations in overweight and obese European young adults. Eur J Nutr 2009;48:107-114
92. Zhou X-R, Sun C-H, Liu J-R, Zhao D. Dietary conjugated linoleic acid increases PPARgamma gene expression in adipose tissue of obese rat, and improves insulin resistance. Growth Horm IGF Res 2008;18:361-368
93. Kang K, Pariza MW. Trans-10, cis-12 conjugated linoleic acid reduces leptin secretion from 3T3-L1 adipocytes. Biochem Biophys Res Commun 2001;287:377-382
94. Jang EM, Choi M-S, Jung UJ, et al. Beneficial effects of curcumin on hyperlipidemia and insulin resistance in high-fat-fed hamsters. Metabolism 2008;57:1576-1583
95. Na XR, Ezaki J, Sugiyama F, et al. Isoflavone regulates lipid metabolism via expression of related genes in OVX rats fed on a high-fat diet. Biomed Environ Sci 2008;21:357-364
96. Rivera L, Morón R, Zarzuelo A, Galisteo M. Long-term resveratrol administration reduces metabolic disturbances and lowers blood pressure in obese Zucker rats. Biochem Pharmacol 2009;77:1053-1063
97. Shih XC, Lin C-H, Lin W-L, Wu J-B. Momordica charantia extract on insulin resistance and the skeletal muscle GLUT3 protein in fructose-fed rats. J Ethnopharmacol 2009;123:82-90
98. Miyazaki Y, DeFronzo RA. Rosiglitazone and pioglitazone similarly improve insulin sensitivity and secretion, glucose tolerance and adipocytokines in Type 2 diabetic patients. Diab Obes Metab 2008;10:1204-1211
99. Oz O, Tuncel E, Eryilmaz S, et al. Arterial elasticity and plasma levels of adiponectin and leptin in Type 2 diabetic patients treated with thiazolidinediones. Endocrine 2008;33:101-105
100. Sharma PK, Bhansali A, Sialy R, et al. Effects of pioglitazone and metformin on plasma adiponectin in newly detected Type 2 diabetes mellitus. Clin Endocrinol 2006;65:722-728
101. Bouskila M, Pajvani UP, Scherer PE. Adiponectin: a relevant player in PPARgamma-agonist-mediated imporve1ments in hepatic insulin sensitivity? Int J Obesity 2005;29:S17-23
102. Combs TP, Wagner JA, Berger J, et al. Induction of adipocyte complement-related protein of 30 kilodaltons by PPARgamma agonists: a potential mechanism of insulin sensitization. Endocrinology 2002;143:998-1007
103. Komorowski J, Stepien H. The role of the endocannabinoid system in the regulation of endocrine function and in the control of energy balance in humans. Postepy Hig Med Dosw 2007;61:99-105
104. Poirier B, Bidouard JP, Cadrouvele C, et al. The anti-obesity effect of rimonabant is associated with an improved serum lipid profile. Diab Obes Metab 2005;7:65-72
105. Sarnataro D, Pisanti S, Santoro A, et al. The cannabinoid CB1 receptor antagonist Rimonabant (SR141716) inhibits human breast cancer cell proliferation through a lipid raft-mediated mechanism. Mol Pharmacol 2006;70:1298-1306
106. Guerre-Millo M. Adiponectin: an update. Diabetes 2008;34:12-18