The Role of Leptin in Cancer Pathogenesis


Leptin is a hormone produced and secreted by adipose tissue. It is a member of adipokine family with a principal role in body weight regulation. It is reported that low brain leptin levels enhance the activity of hypothalamic orexigenic signals promoting feeding and suppressing energy expenditure and vice versa. Moreover, leptin via its three receptors participates in multiple neuroendocrine loops regulation. Serum leptin levels are positively associated with BMI (Body Mass Index) and whilst interact not only with other cytokines but also with serum insulin and cortisol levels. The aim of the present review is to study the role of leptin in carcinogenesis and its implications in cancer-related systemic inflammation.

Share and Cite:

I. Tourkantonis, M. Kiagia, E. Peponi, S. Tsagouli and K. Syrigos, "The Role of Leptin in Cancer Pathogenesis," Journal of Cancer Therapy, Vol. 4 No. 2, 2013, pp. 640-650. doi: 10.4236/jct.2013.42080.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Y. Zhang, R. Proenca, M. Maffei, M. Barone, L. Leopold and J. M. Friedman, “Positional Cloning of the Mouse Obese Gene and Its Human Homologue,” Nature, Vol. 372, No. 6505, 1994, pp. 425-432. doi:10.1038/372425a0
[2] M. Baratta, “Leptin—From a Signal of Adiposity to a Hormonal Mediator in Peripheral Tissues,” Medical Science Monitor, Vol. 8, No. 12, 2002, pp. 282-292.
[3] J. F. Caro, M. K. Sinha, J. W. Kolaczynski, P. L. Zhang and R. V. Considine, “Leptin: The Tale of an Obesity Gene,” Diabetes, Vol. 45, No. 11, 1996, pp. 1455-1462.
[4] J. Webber, “Energy Balance in Obesity,” Proceedings of the Nutrition Society, Vol. 62, No. 2, 2003, pp. 539-543. doi:10.1079/PNS2003256
[5] P. Trayhurn, N. Hoggard, J. G. Mercer and D. V. Rayner, “Leptin: Fundamental Aspects,” International Journal of Obesity, Vol. 23, Suppl. 1, 1999, pp. 22-28. doi:10.1038/sj.ijo.0800791
[6] P. C. Tsiotra, V. Pappa, S. A. Raptis and C. Tsigos, “Expression of the Long and Short Leptin Receptor Isoforms in Peripheral Blood Mononuclear Cells: Implications for Leptin’s Actions,” Metabolism: Clinical and Experimental, Vol. 49, No. 12, 2000, pp. 1537-1541. doi:10.1053/meta.2000.18519
[7] A. Lammert, W. Kiess, A. Bottner, A. Glasow and J. Kratzsch, “Soluble Leptin Receptor Represents the Main Leptin Binding Activity in Human Blood,” Biochemical and Biophysical Research Communications, Vol. 283, No. 4, 2001, pp. 982-988. doi:10.1006/bbrc.2001.4885
[8] A. M. Wallace, “Measurement of Leptin and Leptin Binding in the Human Circulation,” Annals of Clinical Biochemistry, Vol. 37, No. 3, 2000, pp. 244-252. doi:10.1258/0004563001899311
[9] N. Ghilardi, S. Ziegler, A. Wiestner, R. Stoffel, M. H. Heim and R. C. Skoda, “Defective STAT Signaling by the Leptin Receptor in Diabetic Mice,” Proceedings of the National Academy of Sciences, Vol. 93, No. 13, 1996, pp. 6231-6235. doi:10.1073/pnas.93.13.6231
[10] G. Frühbeck, “A Heliocentric View of Leptin,” Proceedings of the Nutrition Society, Vol. 60, No. 3, 2001, pp. 301-318. doi:10.1079/PNS200196
[11] M. Rosická, M. Krsek, M. Matoulek, Z. Jarkovská, J. Marek, V. Justová, et al., “Serum Ghrelin Levels in Obese Patients: The Relationship to Serum Leptin Levels and Soluble Leptin Receptors Levels,” Physiological Research, Vol. 52, No. 1, 2003, pp. 61-66.
[12] S. B. Heymsfield, A. S. Greenberg, K. Fujioka, R. M. Dixon, R. Kushner, T. Hunt, et al., “Recombinant Leptin for Weight Loss in Obese and Lean Adults: A Randomized, Controlled, Dose-Escalation Trial,” JAMA: The Journal of the American Medical Association, Vol. 282, No. 16, 1999, pp. 1568-1575. doi:10.1001/jama.282.16.1568
[13] K. El-Haschimi, D. D. Pierroz, S. M. Hileman, C. Bjorbak and J. S. Flier, “Two Defects Contribute to Hypothalamic Leptin Resistance in Mice with Diet-Induced Obesity,” The Journal of Clinical Investigation, Vol. 105, No. 12, 2000, pp. 1827-1832. doi:10.1172/JCI9842
[14] C. Bjorbok, S. Uotani, B. da Silva and J. S. Flier, “Divergent Signaling Capacities of the Long and Short Isoforms of the Leptin Receptor,” Journal of Biological Chemistry, Vol. 272, No. 51, 1997, pp. 32686-32695. doi:10.1074/jbc.272.51.32686
[15] C. Liu, X.-J. Liu, G. Barry, N. Ling, R. A. Maki and E. B. De Souza, “Expression and Characterization of a Putative High Affinity Human Soluble Leptin Receptor,” Endocrinology, Vol. 138, No. 8, 1997, pp. 3548-3554. doi:10.1210/en.138.8.3548
[16] L. Huang, Z. Wang and C. Li, “Modulation of Circulating Leptin Levels by Its Soluble Receptor,” Journal of Biological Chemistry, Vol. 276, No. 9, 2001, pp. 6343-6349. doi:10.1074/jbc.M009795200
[17] R. Devos, Y. Guisez, J. Van der Heyden, D. W. White, M. Kalai, M. Fountoulakis, et al., “Ligand-Independent Dimerization of the Extracellular Domain of the Leptin Receptor and Determination of the Stoichiometry of Leptin Binding,” Journal of Biological Chemistry, Vol. 272, No. 29, 1997, pp. 18304-18310. doi:10.1074/jbc.272.29.18304
[18] G. Yang, H. Ge, A. Boucher, X. Yu and C. Li, “Modulation of Direct Leptin Signaling by Soluble Leptin Receptor,” Molecular Endocrinology, Vol. 18, No. 6, 2004, pp. 1354-1362. doi:10.1210/me.2004-0027
[19] O. Zastrow, B. Seidel, W. Kiess, J. Thiery, E. Keller, A. Battner, et al., “The Soluble Leptin Receptor Is Crucial for Leptin Action: Evidence from Clinical and Experimental Data,” International Journal of Obesity, Vol. 27, No. 12, 2003, pp. 1472-1478. doi:10.1038/sj.ijo.0802432
[20] J. Licinio, C. Mantzoros, A. B. Negrao, G. Cizza, M. L. Wong, P. B. Bongiorno, et al., “Human Leptin Levels Are Pulsatile and Inversely Related to Pituitary-Adrenal Function,” Nature Medicine, Vol. 3, No. 5, 1997, pp. 575-579. doi:10.1038/nm0597-575
[21] M. K. Sinha, J. P. Ohannesian, M. L. Heiman, A. Kriauciunas, T. W. Stephens, S. Magosin, et al., “Nocturnal Rise of Leptin in Lean, Obese, and Non-Insulin-Dependent Diabetes Mellitus Subjects,” The Journal of Clinical Investigation, Vol. 97, No. 5, 1996, pp. 1344-1347. doi:10.1172/JCI118551
[22] R. V. Considine, M. K. Sinha, M. L. Heiman, A. Kriauciunas, T. W. Stephens, M. R. Nyce, et al., “Serum Immunoreactive-Leptin Concentrations in Normal-Weight and Obese Humans,” New England Journal of Medicine, Vol. 334, No. 5, 1996, pp. 292-295. doi:10.1056/NEJM199602013340503
[23] R. S. Ahima, D. Prabakaran, C. Mantzoros, D. Qu, B. Lowell, E. Maratos-Flier, et al., “Role of Leptin in the Neuroendocrine Response to Fasting,” Nature, Vol. 382, No. 6588, 1996, pp. 250-252. doi:10.1038/382250a0
[24] P. Koutkia, B. Canavan, M. L. Johnson, A. DePaoli and S. Grinspoon, “Characterization of Leptin Pulse Dynamics and Relationship to Fat Mass, Growth Hormone, Cortisol, and Insulin,” American Journal of Physiology—Endocrinology and Metabolism, Vol. 285, No. 2, 2003, pp. E372-E379.
[25] L. J. Slieker, K. W. Sloop, P. L. Surface, A. Kriauciunas, F. LaQuier, J. Manetta, et al., “Regulation of Expression of ob mRNA and Protein by Glucocorticoids and cAMP,” Journal of Biological Chemistry, Vol. 271, No. 10, 1996, pp. 5301-5304. doi:10.1074/jbc.271.10.5301
[26] S. French and K. Castiglione, “Recent Advances in the Physiology of Eating,” Proceedings of the Nutrition Society, Vol. 61, No. 4, 2002, pp. 489-496. doi:10.1079/PNS2002190
[27] C. K. Welt, J. L. Chan, J. Bullen, R. Murphy, P. Smith, A. M. DePaoli, et al., “Recombinant Human Leptin in Women with Hypothalamic Amenorrhea,” New England Journal of Medicine, Vol. 351, No. 10, 2004, pp. 987-997. doi:10.1056/NEJMoa040388
[28] F. F. Chehab, J. Qiu, K. Mounzih, A. Ewart-Toland and S. Ogus, “Leptin and Reproduction,” Nutrition Reviews, Vol. 60, 2002, pp. S39-S46. doi:10.1301/002966402320634823
[29] J. M. Friedman and J. L. Halaas, “Leptin and the Regulation of Body Weight in Mammals,” Nature, Vol. 395, No. 6704, 1998, pp. 763-770. doi:10.1038/27376
[30] A. Sainsbury, G. J. Cooney and H. Herzog, “Hypothalamic Regulation of Energy Homeostasis,” Best Practice & Research Clinical Endocrinology & Metabolism, Vol. 16, No. 4, 2002, pp. 623-637. doi:10.1053/beem.2002.0230
[31] Y. Y. Chan, D. K. Clifton and R. A. Steiner, “Role of NPY Neurones in GH-Dependent Feedback Signalling to the Brain,” Hormone Research, Vol. 45, Suppl. 1, 1996, pp. 12-14. doi:10.1159/ 000184820
[32] D. D. Pierroz, A. C. Aebi, I. T. Huhtaniemi and M. L. Aubert, “Many LH Peaks Are Needed to Physiologically Stimulate Testosterone Secretion: Modulation by Fasting and NPY,” American Journal of Physiology—Endocrinology and Metabolism, Vol. 276, No. 4, 1999, pp. E603-E610.
[33] F. Rohner-Jeanrenaud, “Aspects of the Neuroendocrine Regulation of Body Weight Homeostasis,” Annales D Endocrinologie, Vol. 63, No. 2, 2002, pp. 125-128.
[34] J. S. Flier, “Leptin Expression and Action: New Experimental Paradigms,” Proceedings of the National Academy of Sciences, Vol. 94, No. 9, 1997, pp. 4242-4245. doi:10.1073/pnas.94.9.4242
[35] W. A. Banks, “The Many Lives of Leptin,” Peptides, Vol. 25, No. 3, 2004, pp. 331-338. doi:10.1016/j.pep tides.2004.02.014
[36] G. L. Carlson, M. Saeed, R. A. Little and M. H. Irving, “Serum Leptin Concentrations and Their Relation to Metabolic Abnormalities in Human Sepsis,” American Journal of Physiology—Endocrinology and Metabolism, Vol. 276, No. 4, 1999, pp. E658-E62.
[37] A. G. W. Moses, N. Dowidar, B. Holloway, I. Waddell, K. C. H. Fearon and J. A. Ross, “Leptin and Its Relation to Weight Loss, ob Gene Expression and the Acute-Phase Response in Surgical Patients,” British Journal of Surgery, Vol. 88, No. 4, 2001, pp. 588-593. doi:10.1046/j.1365-2168.2001.01743.x
[38] N. Takabatake, H. Nakamura, O. Minamihaba, M. Inage, S. Inoue, S. Kagaya, et al., “A Novel Pathophysiologic Phenomenon in Cachexic Patients with Chronic Obstructive Pulmonary Disease,” American Journal of Respiratory and Critical Care Medicine, Vol. 163, No. 6, 2001, pp. 1314-1319. doi:10.1164/ajrccm.163.6.2004175
[39] A. M. Schols, E. C. Creutzberg, W. A. Buurman, L. A. Campfield, W. H. Saris and E. F. Wouters, “Plasma Leptin Is Related to Proinflammatory Status and Dietary Intake in Patients with Chronic Obstructive Pulmonary Disease,” American Journal of Respiratory and Critical Care Medicine, Vol. 160, No. 4, 1999, pp. 1220-1226. doi:10.1164/ajrccm.160.4.9811033
[40] M. R. Alemán, F. Santolaria, N. Batista, M. J. de La Vega, E. González-Reimers, A. Milena, et al., “Leptin Role in Advanced Lung Cancer. A Mediator of the Acute Phase Response or a Marker of the Status of Nutrition?” Cytokine, Vol. 19, No. 1, 2002, pp. 21-26. doi:10.1006/cyto.2002.1051
[41] J. Simons, A. Schols, L. Campfield, E. Wouters and W. Saris, “Plasma Concentration of Total Leptin and Human Lung-Cancer-Associated Cachexia,” Clinical Science, Vol. 93, No. 3, 1997, pp. 273-277.
[42] D. R. Brown, D. E. Berkowitz and M. J. Breslow, “Weight Loss Is Not Associated with Hyperleptinemia in Humans with Pancreatic Cancer,” Journal of Clinical Endocrinology & Metabolism, Vol. 86, No. 1, 2001, pp. 162-166. doi:10.1210/jc.86.1.162
[43] E. M. Karapanagiotou, E. A. Tsochatzis, K. D. Dilana, I. Tourkantonis, I. Gratsias and K. N. Syrigos, “The Significance of Leptin, Adiponectin, and Resistin Serum Levels in Non-Small Cell Lung Cancer (NSCLC),” Lung cancer, Vol. 61, No. 3, 2008, pp. 391-397. doi:10.1016/j.lungcan.2008.01.018
[44] A. M. Wallace, N. Sattar and D. C. McMillan, “Effect of Weight Loss and the Inflammatory Response on Leptin Concentrations in Gastrointestinal Cancer Patients,” Clinical Cancer Research, Vol. 4, No. 12, 1998, pp. 2977-2979.
[45] G. Mantovani, A. Macciò, L. Mura, E. Massa, M. C. Mudu, C. Mulas, et al., “Serum Levels of Leptin and Proinflammatory Cytokines in Patients with AdvancedStage Cancer at Different Sites,” Journal of Molecular Medicine, Vol. 78, No. 10, 2000, pp. 554-561. doi:10.1007/s001090000137
[46] E. E. Calle, C. Rodriguez, K. Walker-Thurmond and M. J. Thun, “Overweight, Obesity, and Mortality from Cancer in a Prospectively Studied Cohort of US Adults,” New England Journal of Medicine, Vol. 348, No. 17, 2003, pp. 1625-1638. doi:10.1056/NEJMoa021423
[47] K. K. Carroll, “Obesity as a Risk Factor for Certain Types of Cancer,” Lipids, Vol. 33, No. 11, 1998, pp. 1055-1059. doi:10.1007/s11745-998-0305-8
[48] P. Somasundar, D. W. McFadden, S. M. Hileman and L. Vona-Davis, “Leptin Is a Growth Factor in Cancer,” The Journal of Surgical Research, Vol. 116, No. 2, 2004, pp. 337-349. doi:10.1016/j.jss. 2003.09.004
[49] M. R. Sierra-Honigmann, A. K. Nath, C. Murakami, G. García-Cardena, A. Papapetropoulos, W. C. Sessa, et al., “Biological Action of Leptin as an Angiogenic Factor,” Science, Vol. 281, No. 5383, 1998, pp. 1683-1686. doi:10.1126/science.281.5383.1683
[50] A. Bouloumié, H. C. A. Drexler, M. Lafontan and R. Busse, “Leptin, the Product of Ob Gene, Promotes Angiogenesis,” Circulation Research, Vol. 83, No. 10, 1998, pp. 1059-1066. doi:10.1161/01. RES.83.10.1059
[51] S. K. Smith, “Regulation of Angiogenesis in the Endometrium,” TEM, Trends in Endocrinology and Metabolism, Vol. 12, No. 4, 2001, pp. 147-151. doi:10.1016/S1043-2760(01)00379-4
[52] J. Spranger and A. F. Pfeiffer, “New Concepts in Pathogenesis and Treatment of Diabetic Retinopathy,” Experimental and Clinical Endocrinology & Diabetes, Vol. 109, Suppl. 2, 2001, pp. S438-S450. doi:10.1055/s-2001-18601
[53] J. Folkman, “What Is the Evidence That Tumors Are Angiogenesis Dependent?” Journal of the National Cancer Institute, Vol. 82, No. 1, 1990, pp. 4-7. doi:10.1093/jnci/82.1.4
[54] D. P. Rose and J. M. Connolly, “Regulation of Tumor Angiogenesis by Dietary Fatty Acids and Eicosanoids,” Nutrition and Cancer, Vol. 37, No. 2, 2000, pp. 119-127. doi:10.1207/S1532791 4NC372_1
[55] H. Y. Park, H. M. Kwon, H. J. Lim, B. K. Hong, J. Y. Lee, B. E. Park, et al., “Potential Role of Leptin in Angiogenesis: Leptin Induces Endothelial Cell Proliferation and Expression of Matrix Metalloproteinases in Vivo and in Vitro,” Experimental & Molecular Medicine, Vol. 33, No. 2, 2001, pp. 95-102. doi:10.1038/emm.2001.17
[56] M. Artwohl, M. Roden, T. H?lzenbein, A. Freudenthaler, W. Waldh?usl and S. M. Baumgartner-Parzer, “Modulation by Leptin of Proliferation and Apoptosis in Vascular Endothelial Cells,” International Journal of Obesity and Related Metabolic Disorders, Vol. 26, No. 4, 2002, pp. 577-580. doi:10.1038/sj.ijo.0801947
[57] R. Cao, E. Brakenhielm, C. Wahlestedt, J. Thyberg and Y. Cao, “Leptin Induces Vascular Permeability and Synergistically Stimulates Angiogenesis with FGF-2 and VEGF,” Proceedings of the National Academy of Sciences, Vol. 98, No. 11, 2001, pp. 6390-6395. doi:10.1073/pnas.101564798
[58] D. Ribatti, B. Nico, A. S. Belloni, A. Vacca, L. Roncali and G. G. Nussdorfer, “Angiogenic Activity of Leptin in the Chick Embryo Chorioallantoic Membrane Is in Part Mediated by Endogenous Fibroblast Growth Factor-2,” International Journal of Molecular Medicine, Vol. 8, No. 3, 2001, pp. 265-268.
[59] W. Stetler-Stevenson, “The Role of Matrix Metalloproteinases in Tumor Invasion, Metastasis, and Angiogenesis,” Surgical Oncology Clinics of North America, Vol. 10, No. 2, 2001, pp. 383-392.
[60] Y. Chilliard, M. Bonnet, C. Delavaud, Y. Faulconnier, C. Leroux, J. Djiane, et al., “Leptin in Ruminants. Gene Expression in Adipose Tissue and Mammary Gland, and Regulation of Plasma Concentration,” Domestic Animal Endocrinology, Vol. 21, No. 4, 2001, pp. 271-295. doi:10.1016/S0739-7240(01)00124-2
[61] S. N. O’Brien, B. H. Welter and T. M. Price, “Presence of Leptin in Breast Cell Lines and Breast Tumors,” Biochemical and Biophysical Research Communications, Vol. 259, No. 3, 1999, pp. 695-698. doi:10.1006/bbrc.1999.0843
[62] D. A. Magoffin, S. R. Weitsman, S. K. Aagarwal and A. J. Jakimiuk, “Leptin Regulation of Aromatase Activity in Adipose Stromal Cells from Regularly Cycling Women,” Ginekologia Polska, Vol. 70, No. 1, 1999, pp. 1-7.
[63] P. J. Goodwin, M. Ennis, K. I. Pritchard, M. E. Trudeau, J. Koo, Y. Madarnas, et al., “Fasting Insulin and Outcome in Early-Stage Breast Cancer: Results of a Prospective Cohort Study,” Journal of Clinical Oncology, Vol. 20, No. 1, 2002, pp. 42-51. doi:10.1200/JCO.20.1.42
[64] H. Askari, J. Liu and S. Dagogo-Jack, “Hormonal Regulation of Human Leptin in Vivo: Effects of Hydrocortisone and Insulin,” International Journal of Obesity and Related Metabolic Disorders, Vol. 24, No. 10, 2000, pp. 1254-1259. doi:10.1038/sj.ijo.0801379
[65] K. Laud, I. Gourdou, L. Pessemesse, J. P. Peyrat and J. Djiane, “Identification of Leptin Receptors in Human Breast Cancer: Functional Activity in the T47-D Breast Cancer Cell Line,” Molecular and Cellular Endocrinology, Vol. 188, No. 1-2, 2002, pp. 219-226. doi:10.1016/S0303-7207(01)00678-5
[66] M.-N. Dieudonne, F. Machinal-Quelin, V. Serazin-Leroy, M.-C. Leneveu, R. Pecquery and Y. Giudicelli, “Leptin Mediates a Proliferative Response in Human MCF7 Breast Cancer Cells,” Biochemical and Biophysical Research Communications, Vol. 293, No. 1, 2002, pp. 622-628. doi:10.1016/S0006-291X(02)00205-X
[67] K. Engels, S. B. Fox and A. L. Harris, “Angiogenesis as a Biologic and Prognostic Indicator in Human Breast Carcinoma,” Experientia Supplementum, Vol. 79, No. 1, 1997, pp. 113-156. doi:10.1007/978-3-0348-9006-9_6
[68] M. Toi, K. Inada, H. Suzuki and T. Tominaga, “Tumor Angiogenesis in Breast Cancer: Its Importance as a Prognostic Indicator and the Association with Vascular Endothelial Growth Factor Expression,” Breast Cancer Research and Treatment, Vol. 36, No. 2, 1995, pp. 193-204. doi:10.1007/BF00666040
[69] B. K. Linderholm, T. Lindahl, L. Holmberg, S. Klaar, J. Lennerstrand, R. Henriksson, et al., “The Expression of Vascular Endothelial Growth Factor Correlates with Mutant P53 and Poor Prognosis in Human Breast Cancer,” Cancer Research, Vol. 61, No. 5, 2001, pp. 2256-2260.
[70] S. D. Hursting, S. N. Perkins, J. M. Phang and J. C. Barrett, “Diet and Cancer Prevention Studies in P53-Deficient Mice,” The Journal of Nutrition, Vol. 131, No. 11, 2001, pp. 3092S-3094S.
[71] D. P. Rose, E. M. Gilhooly and D. W. Nixon, “Adverse Effects of Obesity on Breast Cancer Prognosis, and the Biological Actions of Leptin (Review),” International Journal of Oncology, Vol. 21, No. 6, 2002, pp. 1285-1292.
[72] P. Somasundar, L. C. Vona-Davis, D. Riggs, B. Jackson and D. W. McFadden, “COX-2 Inhibition Reverses LeptinStimulated Breast Cancer Growth in Vitro,” Gastroenterology, Vol. 124, No. 4, 2003, p. A611. doi:10.1016/S0016-5085(03)83096-2
[73] C. Garofalo, D. Sisci and E. Surmacz, “Leptin Interferes with the Effects of the Antiestrogen ICI 182, 780 in MCF-7 Breast Cancer Cells,” Clinical Cancer Research, Vol. 10, No. 19, 2004, pp. 6466-6475. doi:10.1158/1078-0432.CCR-04-0203
[74] L. Vona-Davis and D. P. Rose, “Adipokines as Endocrine, Paracrine, and Autocrine Factors in Breast Cancer Risk and Progression,” Endocrine-Related Cancer, Vol. 14, No. 2, 2007, pp. 189-206. doi:10.1677/ERC-06-0068
[75] A. Macciò, C. Madeddu, G. Gramignano, C. Mulas, C. Floris, D. Massa, et al., “Correlation of Body Mass Index and Leptin with Tumor Size and Stage of Disease in Hormone-Dependent Postmenopausal Breast Cancer: Preliminary Results and Therapeutic Implications,” Journal of Molecular Medicine, Vol. 88, No. 7, 2010, pp. 677-686. doi:10.1007/s00109-010-0611-8
[76] D. P. Rose, D. Komninou and G. D. Stephenson, “Obesity, Adipocytokines, and Insulin Resistance in Breast Cancer,” Obesity Reviews, Vol. 5, No. 3, 2004, pp. 153-165. doi:10.1111/j.1467-789X.2004.00142.x
[77] P. Somasundar, K. A. Frankenberry, H. Skinner, G. Vedula, D. W. McFadden, D. Riggs, et al., “Prostate Cancer cell Proliferation Is Influenced by Leptin,” The Journal of Surgical Research, Vol. 118, No. 1, 2004, pp. 71-82. doi:10.1016/j.jss.2004.01.017
[78] P. Lagiou, L. B. Signorello, D. Trichopoulos, A. Tzonou, A. Trichopoulou and C. S. Mantzoros, “Leptin in Relation to Prostate Cancer and Benign Prostatic Hyperplasia,” International Journal of Cancer, Vol. 76, No. 1, 1998, pp. 25-28. doi:10.1002/(SICI)1097-0215(19980330)76:1<25::AID-IJC5>3.0.CO;2-#
[79] S. Chang, S. D. Hursting, J. H. Contois, S. S. Strom, Y. Yamamura, R. J. Babaian, et al., “Leptin and Prostate Cancer,” The Prostate, Vol. 46, No. 1, 2001, pp. 62-67. doi:10.1002/1097-0045(200101)46:1<62::AID-PROS1009>3.0.CO;2-V
[80] P. Stattin, S. Soderberg, G. Hallmans, A. Bylund, R. Kaaks, U.-H. Stenman, et al., “Leptin Is Associated with Increased Prostate Cancer Risk: A Nested Case-Referent Study,” The Journal of Clinical Endocrinology & Metabolism, Vol. 86, No. 3, 2001, pp. 1341-1345. doi:10.1210/jc.86.3.1341
[81] A. W. Hsing, S. Chua, Y.-T. Gao, E. Gentzschein, L. Chang, J. Deng, et al., “Prostate Cancer Risk and Serum Levels of Insulin and Leptin: A Population-Based Study,” Journal of the National Cancer Institute, Vol. 93, No. 10, 2001, pp. 783-789. doi:10.1093/jnci/93.10.783
[82] H. Li, M. J. Stampfer, L. Mucci, N. Rifai, W. Qiu, T. Kurth, et al., “A 25-Year Prospective Study of Plasma Adiponectin and Leptin Concentrations and Prostate Cancer Risk and Survival,” Clinical Chemistry, Vol. 56, No. 1, 2010, pp. 34-43. doi:10.1373/clinchem.2009.133272
[83] R. Ribeiro, A. Vasconcelos, S. Costa, D. Pinto, A. Morais, J. Oliveira, et al., “Overexpressing Leptin Genetic Polymorphism (?2548 G/A) Is Associated with Susceptibility to Prostate Cancer and Risk of Advanced Disease,” The Prostate, Vol. 59, No. 3, 2004, pp. 268-274. doi:10.1002/pros.20004
[84] S. J. Freedland and E. A. Platz, “Obesity and Prostate Cancer: Making Sense out of Apparently Conflicting Data,” Epidemiologic Reviews, Vol. 29, No. 1, 2007, pp. 88-97. doi:10.1093/ep irev/mxm006
[85] C. A. Baile, M. A. Della-Fera and R. J. Martin, “Regulation of Metabolism and Body Fat Mass by Leptin,” Annual Review of Nutrition, Vol. 20, No. 1, 2000, pp. 105-127. doi:10.1146/annurev.nutr.20.1.105
[86] X. Lin, M. R. Chavez, R. C. Bruch, G. E. Kilroy, L. A. Simmons, L. Lin, et al., “The Effects of a High Fat Diet on Leptin mRNA, Serum Leptin and the Response to Leptin Are Not Altered in a Rat Strain Susceptible to High Fat Diet-Induced Obesity,” The Journal of Nutrition, Vol. 128, No. 10, 1998, pp. 1606-1613.
[87] D. S. Alberts, J. Einspahr, S. Rees-McGee, P. Ramanujam, M. K. Buller, L. Clark, et al., “Effects of Dietary Wheat Bran Fiber on Rectal Epithelial Cell Proliferation in Patients with Research for Colorectal Cancers,” Journal of the National Cancer Institute, Vol. 82, No. 15, 1990, pp. 1280-1285. doi:10.1093/jnci/82.15.1280
[88] C. Liew, H. A. J. Schut, S. F. Chin, M. W. Pariza and R. H. Dashwood, “Protection of Conjugated Linoleic Acids against 2-Amino-3-methylimidazo[4,5-f]quinoline-iduced Colon Carcinogenesis in the F344 Rat: A Study of Inhibitory Mechanisms,” Carcinogenesis, Vol. 16, No. 12, 1995, pp. 3037-3043. doi:10.1093/carcin/16.12.3037
[89] S. M. Rahman, Y.-M. Wang, H. Yotsumoto, J.-Y. Cha, S.-Y. Han, S. Inoue, et al., “Effects of Conjugated Linoleic Acid on Serum Leptin Concentration, Body-Fat Accumulation, and β-Oxidation of Fatty Acid in OLETF Rats,” Nutrition (Burbank, Los Angeles County, Calif), Vol. 17, No. 5, 2001, pp. 385-390. doi:10.1016/S0899-9007(00)00584-0
[90] N. F. Chu, M. J. Stampfer, D. Spiegelman, N. Rifai, G. S. Hotamisligil and E. B. Rimm, “Dietary and Lifestyle Factors in Relation to Plasma Leptin Concentrations among Normal Weight and Overweight Men,” International Journal of Obesity and Related Metabolic Disorders, Vol. 25, No. 1, 2001, pp. 106-114. doi:10.1038/sj.ijo.0801468
[91] J. C. H. Hardwick, G. R. Van Den Brink, G. J. Offerhaus, S. J. H. Van Deventer and M. P. Peppelenbosch, “Leptin Is a Growth Factor for Colonic Epithelial Cells,” Gastroenterology, Vol. 121, No. 1, 2001, pp. 79-90. doi:10.1053/gast.2001.25490
[92] P. Stattin, A. Lukanova, C. Biessy, S. Soderberg, R. Palmqvist, R. Kaaks, et al., “Obesity and Colon Cancer: Does Leptin Provide a Link?” International Journal of Cancer, Vol. 109, No. 1, 2004, pp. 149-152. doi:10.1002/ijc.11668
[93] P. Stattin, R. Palmqvist, S. Soderberg, C. Biessy, B. Ardnor, G. Hallmans, et al., “Plasma Leptin and Colorectal Cancer Risk: A Prospective Study in Northern Sweden,” Oncology Reports, Vol. 10, No. 6, 2003, pp. 2015-2021.
[94] K. Tamakoshi, H. Toyoshima, K. Wakai, M. Kojima, K. Suzuki, Y. Watanabe, et al., “Leptin Is Associated with an Increased Female Colorectal Cancer Risk: A Nested Case-Control Study in Japan,” Oncology, Vol. 68, No. 4-6, 2005, pp. 454-461. doi:10.1159/000086988
[95] T. E. Nakajima, Y. Yamada, T. Hamano, K. Furuta, T. Matsuda, S. Fujita, et al., “Adipocytokines as New Promising Markers of Colorectal Tumors: Adiponectin for Colorectal Adenoma, and Resistin and Visfatin for Colorectal Cancer,” Cancer Science, Vol. 101, No. 5, 2010, pp. 1286-1291. doi:10.1111/j.1349-7006.2010.01518.x
[96] L. Tessitore, B. Vizio, O. Jenkins, I. De Stefano, C. Ritossa, J. M. Argiles, et al., “Leptin Expression in Colorectal and Breast Cancer Patients,” International Journal of Molecular Medicine, Vol. 5, No. 4, 2000, pp. 421-426.
[97] A. Wallace, N. Sattar and D. McMillan, “Effect of Weight Loss and the Inflammatory Response on Leptin Concentrations in Gastrointestinal Cancer Patients,” Clinical Cancer Research, Vol. 4, No. 12, 1998, pp. 2977-2979.
[98] S. Attoub, V. Noe, L. Pirola, E. Bruyneel, E. Chastre, M. Mareel, et al., “Leptin Promotes Invasiveness of Kidney and Colonic Epithelial Cells via Phosphoinositide 3-Kinase-, Rho-, and Rac-Dependent Signaling Pathways,” The FASEB Journal, Vol. 14, No. 14, 2000, pp. 2329-2338. doi:10.1096/fj.00-0162
[99] A. Kumor, P. Daniel, M. Pietruczuk and E. MaleckaPanas, “Serum Leptin, Adiponectin, and Resistin Concentration in Colorectal Adenoma and Carcinoma (CC) Patients,” International Journal of Colorectal Disease, Vol. 24, No. 3, 2009, pp. 275-281. doi:10.1007/s00384-008-0605-y
[100] F. F. Bolukbas, H. Kilic, C. Bolukbas, M. Gumus, M. Horoz, N. Turhal, et al., “Serum Leptin Concentration and Advanced Gastrointestinal Cancers: A Case Controlled Study,” BMC Cancer, Vol. 4, No. 1, 2004, p. 29. doi:10.1186/1471-2407-4-29
[101] M. Koda, M. Sulkowska, L. Kanczuga-Koda, S. Cascio, G. Colucci, A. Russo, et al., “Expression of the Obesity Hormone Leptin and Its Receptor Correlates with Hypoxia-Inducible Factor-1α in Human Colorectal Cancer,” Annals of Oncology, Vol. 18, Suppl. 6, 2007, pp. vi116-vi119. doi:10.1093/annonc/mdm238
[102] S. Paik, S.-M. Jang, K.-S. Jang, K. Lee, D. Choi and S. Jang, “Leptin Expression Correlates with Favorable Clinicopathologic Phenotype and Better Prognosis in Colorectal Adenocarcinoma,” Annals of Surgical Oncology, Vol. 16, No. 2, 2009, pp. 297-303. doi:10.1245/s10434-008-0221-7
[103] T. Azuma, H. Suto, Y. Ito, M. Ohtani, M. Dojo, M. Kuriyama, et al., “Gastric Leptin and Helicobacter Pylori Infection,” GUT, Vol. 49, No. 3, 2001, pp. 324-329. doi:10.1136/gut.49.3.324
[104] R. Pezzilli, A. Barassi, M. M. Corsi, A. M. Morselli-Labate, D. Campana, R. Casadei, et al., “Serum Leptin, but Not Adiponectin and Receptor for Advanced Glycation End Products, Is Able to Distinguish Autoimmune Pancreatitis from Both Chronic Pancreatitis and Pancreatic Neoplasms,” Scandinavian Journal of Gastroenterology, Vol. 45, No. 1, 2010, pp. 93-99. doi:10.3109/00365520903358907
[105] M. Dalamaga, K. Karmaniolas, A. Panagiotou, A. Hsi, J. Chamberland, C. Dimas, et al., “Low Circulating Adiponectin and Resistin, but Not Leptin, Levels Are Associated with Multiple Myeloma Risk: A Case–Control Study,” Cancer Causes Control, Vol. 20, No. 2, 2009, pp. 193-199. doi:10.1007/s10552-008-9233-7
[106] R. Z. Stolzenberg-Solomon, B. I. Graubard, S. Chari, P. Limburg, P. R. Taylor, J. Virtamo, et al., “Insulin, Glucose, Insulin Resistance, and Pancreatic Cancer in Male Smokers,” JAMA: The Journal of the American Medical Association, Vol. 294, No. 22, 2005, pp. 2872-2878. doi:10.1001/jama.294.22.2872
[107] T. Nakajima, Y. Yamada, T. Hamano, K. Furuta, I. Oda, H. Kato, et al., “Adipocytokines and Squamous Cell Carcinoma of the Esophagus,” Journal of Cancer Research and Clinical Oncology, Vol. 136, No. 2, 2010, pp. 261-266. doi:10.1007/s00432-009-0657-6
[108] B. J. Kendall, G. A. Macdonald, N. K. Hayward, J. B. Prins, I. Brown, N. Walker, et al., “Leptin and the Risk of Barrett’s Oesophagus,” GUT, Vol. 57, No. 4, 2008, pp. 448-454. doi:10.1136/gut.2007.131243
[109] D. Diakowska, M. Krzystek-Korpacka, K. MarkockaMaczka, W. Diakowski, M. Matusiewicz and K. Grabowski, “Circulating Leptin and Inflammatory Response in Esophageal Cancer, Esophageal Cancer-Related CachexiaAnorexia Syndrome (CAS) and Non-Malignant CAS of the Alimentary Tract,” Cytokine, Vol. 51, No. 2, 2010, pp. 132-137. doi:10.1016/j.cyto.2010.05.006
[110] E. Petridou, M. Belechri, N. Dessypris, P. Koukoulomatis, E. Diakomanolis, E. Spanos, et al., “Leptin and Body Mass Index in Relation to Endometrial Cancer Risk,” Annals of Nutrition and Metabolism, Vol. 46, No. 3-4, 2002, pp. 147-151. doi:10.1159/000063081
[111] A. Cymbaluk, A. Chudecka-Goaz and I. Rzepka-Górska, “Leptin Levels in Serum Depending on Body Mass Index in Patients with Endometrial Hyperplasia and Cancer,” European Journal of Obstetrics, Gynecology, and Reproductive Biology, Vol. 136, No. 1, 2008, pp. 74-77. doi:10.1016/j.ejogrb. 2006.08.012
[112] A. Lebrecht, E. Ludwig, A. Huber, M. Klein, C. Schneeberger, C. Tempfer, et al., “Serum Vascular Endothelial Growth Factor and Serum Leptin in Patients with Cervical Cancer,” Gynecologic Oncology, Vol. 85, No. 1, 2002, pp. 32-35. doi:10.1006/gyno.2001.6517
[113] T. Nakao, M. Hino, T. Yamane, Y. Nishizawa, H. Morii and N. Tatsumi, “Expression of the Leptin Receptor in Human Leukaemic Blast Cells,” British Journal of Haematology, Vol. 102, No. 3, 1998, pp. 740-745. doi:10.1046/j.1365-2141.1998.00843.x
[114] M. Konopleva, A. Mikhail, Z. Estrov, S. Zhao, D. Harris, G. Sanchez-Williams, et al., “Expression and Function of Leptin Receptor Isoforms in Myeloid Leukemia and Myelodysplastic Syndromes: Proliferative and Anti-Apoptotic Activities,” Blood, Vol. 93, No. 5, 1999, pp. 1668-1676.

Copyright © 2023 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.