Adipocytokines and cancer.

Adipose tissue-produced hormones significantly affect the metabolism of lipids and carbohydrates as well as numerous other processes in human body. It is generally accepted that endocrine dysfunction of adipose tissue may represent one of the causal links between obesity and insulin resistance/diabetes. Epidemiological studies underlined that obesity represents a significant risk factor for the development of cancer, although the exact mechanism of this relationship remains to be determined. Multiple recent studies have indicated that some of adipose tissue-derived hormones may significantly influence the growth and proliferation of tumorous stroma and malignant cells within. Here we review current knowledge about possible relationship of leptin and adiponectin to the etiopathogenesis of different malignant tumors. Most of the studies indicated that while leptin may potentiate the growth of cancer cells in vitro, adiponectin appears to have an opposite effect. Further studies are necessary to decide whether obesity-induced endocrine dysfunction of adipose tissue can directly influence carcinogenesis in different tissues and organs.

[1]  M. Maffei,et al.  Positional cloning of the mouse obese gene and its human homologue , 1994, Nature.

[2]  G A Colditz,et al.  Physical Activity, Obesity, and Risk for Colon Cancer and Adenoma in Men , 1995, Annals of Internal Medicine.

[3]  Philipp E. Scherer,et al.  A Novel Serum Protein Similar to C1q, Produced Exclusively in Adipocytes (*) , 1995, The Journal of Biological Chemistry.

[4]  Rene Devos,et al.  Identification and expression cloning of a leptin receptor, OB-R , 1995, Cell.

[5]  M. Maffei,et al.  Positional cloning of the mouse obese gene and its human homologue , 1995, Nature.

[6]  E. Ravussin,et al.  Leptin levels in human and rodent: Measurement of plasma leptin and ob RNA in obese and weight-reduced subjects , 1995, Nature Medicine.

[7]  B. Lowell,et al.  Expression of ob mRNA and its encoded protein in rodents. Impact of nutrition and obesity. , 1995, The Journal of clinical investigation.

[8]  J. Auwerx,et al.  Transient increase in obese gene expression after food intake or insulin administration , 1995, Nature.

[9]  A. Mikhail,et al.  Novel B219/OB receptor isoforms: Possible role of leptin in hematopoiesis and reproduction , 1996, Nature Medicine.

[10]  Y. Nakano,et al.  Isolation and characterization of GBP28, a novel gelatin-binding protein purified from human plasma. , 1996, Journal of biochemistry.

[11]  B. Jeanrenaud,et al.  The discovery of leptin and its impact in the understanding of obesity. , 1996, European journal of endocrinology.

[12]  T. Funahashi,et al.  cDNA cloning and expression of a novel adipose specific collagen-like factor, apM1 (AdiPose Most abundant Gene transcript 1). , 1996, Biochemical and biophysical research communications.

[13]  C. Mantzoros,et al.  Role of leptin in the neuroendocrine response to fasting , 1996, Nature.

[14]  S. Klein,et al.  Relation between plasma leptin concentration and body fat, gender, diet, age, and metabolic covariates. , 1996, The Journal of clinical endocrinology and metabolism.

[15]  B. Spiegelman,et al.  Adipogenesis and Obesity: Rounding Out the Big Picture , 1996, Cell.

[16]  B. Spiegelman,et al.  AdipoQ Is a Novel Adipose-specific Gene Dysregulated in Obesity (*) , 1996, The Journal of Biological Chemistry.

[17]  H. Koistinen,et al.  Leptin concentration in cord blood correlates with intrauterine growth. , 1997 .

[18]  G. Garcı́a-Cardeña,et al.  Biological action of leptin as an angiogenic factor. , 1998, Science.

[19]  G. Bray,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. , 1998, The Journal of nutrition.

[20]  K. Carroll.  Obesity as a risk factor for certain types of cancer , 1998, Lipids.

[21]  T. Nakao,et al.  Expression of the leptin receptor in human leukaemic blast cells , 1998, British journal of haematology.

[22]  C. Mantzoros,et al.  Leptin in relation to prostate cancer and benign prostatic hyperplasia. , 1998, International Journal of Cancer.

[23]  J. Halaas,et al.  Leptin and the regulation of body weight in mammals , 1998, Nature.

[24]  T. Price,et al.  Presence of leptin in breast cell lines and breast tumors. , 1999, Biochemical and biophysical research communications.

[25]  A. Tuzcu,et al.  The effect of high-fat diet on the development of obesity and serum leptin level in rats , 1999, Eating and weight disorders : EWD.

[26]  C. Mantzoros,et al.  Leptin in relation to carcinoma In situ of the breast: A study of pre‐menopausal cases and controls , 1999, International journal of cancer.

[27]  S. Weitsman,et al.  Leptin regulation of aromatase activity in adipose stromal cells from regularly cycling women. , 1999, Ginekologia polska.

[28]  E. Estey,et al.  Expression and function of leptin receptor isoforms in myeloid leukemia and myelodysplastic syndromes: proliferative and anti-apoptotic activities. , 1999, Blood.

[29]  L. Tessitore,et al.  Leptin expression in colorectal and breast cancer patients. , 2000, International journal of molecular medicine.

[30]  D. Ludwig,et al.  Dietary composition and physiologic adaptations to energy restriction. , 2000, The American journal of clinical nutrition.

[31]  H. Koistinen,et al.  Antiestrogenic tamoxifen and toremifene increase serum leptin levels in postmenopausal breast cancer patients. , 2000, Maturitas.

[32]  J. Kitawaki,et al.  Expression of leptin receptor in human endometrium and fluctuation during the menstrual cycle. , 2000, The Journal of clinical endocrinology and metabolism.

[33]  P. Bischof,et al.  Leptin modulates extracellular matrix molecules and metalloproteinases: possible implications for trophoblast invasion. , 2000, Molecular human reproduction.

[34]  R. Goldbohm,et al.  Anthropometry in relation to prostate cancer risk in the Netherlands Cohort Study. , 2000, American journal of epidemiology.

[35]  T Nakamura,et al.  Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. , 2000, Arteriosclerosis, thrombosis, and vascular biology.

[36]  S. Kihara,et al.  Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages. , 2000, Blood.

[37]  Roy J Martin,et al.  Regulation of metabolism and body fat mass by leptin. , 2000, Annual review of nutrition.

[38]  M. Mareel,et al.  Leptin promotes invasiveness of kidney and colonic epithelial cells via phosphoinositide 3‐kinase‐, Rho‐, and Rac‐dependent signaling pathways , 2000, The FASEB Journal.

[39]  P. Stattin,et al.  Leptin is associated with increased prostate cancer risk: a nested case-referent study. , 2001, The Journal of clinical endocrinology and metabolism.

[40]  S. Chua,et al.  Prostate cancer risk and serum levels of insulin and leptin: a population-based study. , 2001, Journal of the National Cancer Institute.

[41]  H. Adami,et al.  Overweight as an avoidable cause of cancer in Europe , 2001, International journal of cancer.

[42]  A. Ozet,et al.  Effects of tamoxifen on the serum leptin level in patients with breast cancer. , 2001, Japanese journal of clinical oncology.

[43]  H. Watanabe,et al.  High fat diet enhances colonic cell proliferation and carcinogenesis in rats by elevating serum leptin. , 2001, International journal of oncology.

[44]  M. Bonnet,et al.  Leptin in ruminants. Gene expression in adipose tissue and mammary gland, and regulation of plasma concentration. , 2001, Domestic animal endocrinology.

[45]  C. S. Yang,et al.  Tea and prostate cancer. , 2001, Epidemiologic reviews.

[46]  C. Schneeberger,et al.  Serum leptin in patients with vulvar cancer. , 2001, Gynecologic oncology.

[47]  D. Ribatti,et al.  Angiogenic activity of leptin in the chick embryo chorioallantoic membrane is in part mediated by endogenous fibroblast growth factor-2. , 2001, International journal of molecular medicine.

[48]  Ju Yong Lee,et al.  Potential role of leptin in angiogenesis: leptin induces endothelial cell proliferation and expression of matrix metalloproteinases in vivo and in vitro , 2001, Experimental & Molecular Medicine.

[49]  S. Deventer,et al.  Leptin is a growth factor for colonic epithelial cells. , 2001, Gastroenterology.

[50]  M. Spitz,et al.  Leptin and prostate cancer , 2001, The Prostate.

[51]  Y. Terauchi,et al.  The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity , 2001, Nature Medicine.

[52]  R. Janečková.  The role of leptin in human physiology and pathophysiology. , 2001, Physiological research.

[53]  L. Holmberg,et al.  Body weight and colorectal cancer risk in a cohort of Swedish women: relation varies by age and cancer site , 2001, British Journal of Cancer.

[54]  C. Wahlestedt,et al.  Leptin induces vascular permeability and synergistically stimulates angiogenesis with FGF-2 and VEGF , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[55]  D. Trichopoulos,et al.  Leptin and Body Mass Index in Relation to Endometrial Cancer Risk , 2002, Annals of Nutrition and Metabolism.

[56]  Philippe Froguel,et al.  Disruption of Adiponectin Causes Insulin Resistance and Neointimal Formation* , 2002, The Journal of Biological Chemistry.

[57]  T. Tai,et al.  Plasma adiponectin levels in overweight and obese Asians. , 2002, Obesity research.

[58]  D. Rose,et al.  Adverse effects of obesity on breast cancer prognosis, and the biological actions of leptin (review). , 2002, International journal of oncology.

[59]  C. Schneeberger,et al.  Serum vascular endothelial growth factor and serum leptin in patients with cervical cancer. , 2002, Gynecologic oncology.

[60]  S. Uchida,et al.  Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase , 2002, Nature Medicine.

[61]  Jie Deng,et al.  Body size and serum levels of insulin and leptin in relation to the risk of benign prostatic hyperplasia. , 2002, The Journal of urology.

[62]  Xin Hu,et al.  Leptin--a growth factor in normal and malignant breast cells and for normal mammary gland development. , 2003, Journal of the National Cancer Institute.

[63]  J. Peyrat,et al.  Identification of leptin receptors in human breast cancer: functional activity in the T47-D breast cancer cell line , 2002, Molecular and Cellular Endocrinology.

[64]  A. Miller,et al.  Obesity and colorectal cancer risk in women , 2002, Gut.

[65]  M. Lombès,et al.  Brown adipocytes are novel sites of expression and regulation of adiponectin and resistin , 2002, FEBS letters.

[66]  THE CHANGES OF SERUM LEPTIN AND SOLUBLE LEPTIN RECEPTOR LEVELS IN PATIENTS UNDERGOING MOBILIZATION OF PERIPHERAL BLOOD STEM CELLS BEFORE AUTOLOGOUS STEM CELLS TRANSPLANTATION , 2002, Endocrine research.

[67]  H. Onuma,et al.  [Current status of study for type 2 diabetes susceptibility genes]. , 2002, Nihon rinsho. Japanese journal of clinical medicine.

[68]  G. Bray.  The underlying basis for obesity: relationship to cancer. , 2002, The Journal of nutrition.

[69]  Michael J Thun,et al.  Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. , 2003, The New England journal of medicine.

[70]  T. Funahashi,et al.  Genome-wide linkage analysis of serum adiponectin in the Pima Indian population. , 2003, Diabetes.

[71]  S. Kihara,et al.  Association of serum adiponectin levels with breast cancer risk. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[72]  Philippe Froguel,et al.  Cloning of adiponectin receptors that mediate antidiabetic metabolic effects , 2003, Nature.

[73]  A. Partin,et al.  Re: “Obesity and hormone‐dependent tumors: cohort and co‐twin control studies based on the Swedish twin registry” , 2003 .

[74]  A. Wolk,et al.  Obesity and hormone‐dependent tumors: Cohort and co‐twin control studies based on the Swedish Twin Registry , 2003 .

[75]  D. Mcfadden,et al.  Leptin stimulates esophageal adenocarcinoma growth by nonapoptotic mechanisms. , 2003, American journal of surgery.

[76]  D. Mcfadden,et al.  Differential effects of leptin on cancer in vitro. , 2003, The Journal of surgical research.

[77]  R. Eeles,et al.  Association between leptin receptor gene polymorphisms and early‐onset prostate cancer , 2003, BJU international.

[78]  C. Mantzoros,et al.  Plasma adiponectin concentrations in relation to endometrial cancer: a case-control study in Greece. , 2003, The Journal of clinical endocrinology and metabolism.

[79]  R. Pai,et al.  Does leptin promote gastric cancer growth , 2003 .

[80]  Michael D. Trahan,et al.  Does leptin promote gastric cancer growth? , 2003, American Journal of Gastroenterology.

[81]  J. Bełtowski.  Adiponectin and resistin--new hormones of white adipose tissue. , 2003, Medical science monitor : international medical journal of experimental and clinical research.

[82]  A. Wolk,et al.  Obesity and hormone-dependent tumors: cohort and co-twin control studies based on the Swedish Twin Registry. , 2003, International journal of cancer.

[83]  A. Howell,et al.  Central obesity and breast cancer risk: a systematic review , 2003, Obesity reviews : an official journal of the International Association for the Study of Obesity.

[84]  P. Stattin,et al.  Plasma leptin is not associated with prostate cancer risk. , 2003, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[85]  C. Mantzoros,et al.  Adiponectin and breast cancer risk. , 2004, The Journal of clinical endocrinology and metabolism.

[86]  D. Pinto,et al.  Overexpressing leptin genetic polymorphism (−2548 G/A) is associated with susceptibility to prostate cancer and risk of advanced disease , 2004, The Prostate.

[87]  Y. Shang,et al.  Molecular Mechanisms Involved in the Growth Stimulation of Breast Cancer Cells by Leptin , 2004, Cancer Research.

[88]  M. Haluzík,et al.  Adiponectin and its role in the obesity-induced insulin resistance and related complications. , 2004, Physiological research.

[89]  C. Mantzoros,et al.  Circulating adiponectin and endometrial cancer risk. , 2004, The Journal of clinical endocrinology and metabolism.

[90]  E. Giovannucci,et al.  Re: Body size and serum levels of insulin and leptin in relation to the risk of benign prostatic hyperplasia. , 2004, The Journal of urology.

[91]  E. Metter,et al.  Association of prostate cancer risk with insulin, glucose, and anthropometry in the Baltimore longitudinal study of aging. , 2004, Urology.

[92]  Chun‐Hsiung Huang,et al.  Aberrant expression and possible involvement of the leptin receptor in bladder cancer. , 2004, Urology.

[93]  G. Bray,et al.  0021-972X/04/$15.00/0 The Journal of Clinical Endocrinology & Metabolism 89(6):2583–2589 Printed in U.S.A. Copyright © 2004 by The Endocrine Society doi: 10.1210/jc.2004-0535 Medical Consequences of Obesity , 2022 .

[94]  A. Bado,et al.  Leptin Counteracts Sodium Butyrate-induced Apoptosis in Human Colon Cancer HT-29 Cells via NF-κB Signaling* , 2004, Journal of Biological Chemistry.

[95]  D. Mcfadden,et al.  Prostate cancer cell proliferation is influenced by leptin. , 2004, The Journal of surgical research.

[96]  E. Kubista,et al.  Breast cancer size in postmenopausal women is correlated with body mass index and androgen serum levels , 2004, Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology.

[97]  D. Mcfadden,et al.  Leptin induces cell migration and the expression of growth factors in human prostate cancer cells. , 2004, American journal of surgery.

[98]  D. Trichopoulos,et al.  Leptin and insulin growth factor I in relation to breast cancer (Greece) , 2000, Cancer Causes & Control.

[99]  J. Flier,et al.  Adipose Tissue as an Endocrine Organ , 2014 .

[100]  L. Tessitore,et al.  Adipocyte expression and circulating levels of leptin increase in both gynaecological and breast cancer patients. , 2004, International journal of oncology.

[101]  D. Rose,et al.  Obesity, adipocytokines, and insulin resistance in breast cancer , 2004, Obesity reviews : an official journal of the International Association for the Study of Obesity.

[102]  K. Tsai,et al.  Aberrant expression and possible involvement of the leptin receptor in endometrial cancer. , 2004, Gynecologic oncology.

[103]  G. H. Anderson,et al.  Hyperglycemia after protein ingestion concurrent with injection of a GLP-1 receptor agonist in rats: a possible role for dietary peptides. , 2005, American journal of physiology. Regulatory, integrative and comparative physiology.

[104]  Shyi-Jang Shin,et al.  Hypoadiponectinemia Is Associated With Ischemic Cerebrovascular Disease , 2005, Arteriosclerosis, thrombosis, and vascular biology.

[105]  T. Kadowaki,et al.  Adiponectin and adiponectin receptors. , 2005, Endocrine reviews.

[106]  Xavier Palomer,et al.  Adiponectina: un nuevo nexo entre obesidad, resistencia a la insulina y enfermedad cardiovascular , 2005 .

[107]  Antonio Pérez,et al.  [Adiponectin: a new link between obesity, insulin resistance and cardiovascular disease]. , 2005, Medicina clinica.

[108]  B. Yu,et al.  Adiponectin induces growth arrest and apoptosis of MDA-MB-231 breast cancer cell , 2005, Archives of pharmacal research.

[109]  A. Dembińska-kieć,et al.  Visfatin - new adipokine , 2005 .

[110]  P. Leung,et al.  Expression of leptin receptors and potential effects of leptin on the cell growth and activation of mitogen-activated protein kinases in ovarian cancer cells. , 2005, The Journal of clinical endocrinology and metabolism.

[111]  D. Ricquier.  Respiration uncoupling and metabolism in the control of energy expenditure , 2005, The Proceedings of the Nutrition Society.

[112]  Y. Matsuzawa.  White adipose tissue and cardiovascular disease. , 2005, Best practice & research. Clinical endocrinology & metabolism.

[113]  H. Nagawa,et al.  Plasma adiponectin and gastric cancer. , 2005, Clinical cancer research : an official journal of the American Association for Cancer Research.

[114]  M. Matsuda,et al.  Visfatin: a protein secreted by visceral fat that mimics the effects of insulin. , 2005, Science.

[115]  Y. Matsuzawa.  Therapy Insight: adipocytokines in metabolic syndrome and related cardiovascular disease , 2006, Nature Clinical Practice Cardiovascular Medicine.

[116]  Kohjiro Ueki,et al.  Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. , 2006, The Journal of clinical investigation.

[117]  F. Anania,et al.  Leptin promotes the proliferative response and invasiveness in human endometrial cancer cells by activating multiple signal-transduction pathways. , 2006, Endocrine-related cancer.

[118]  Y. Taketani,et al.  Expression of adiponectin receptors and its possible implication in the human endometrium. , 2006, Endocrinology.

[119]  B. Rueda,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)* , 2006, Journal of Biological Chemistry.

[120]  E. Surmacz,et al.  Leptin and cancer , 2006, Journal of cellular physiology.

[121]  J. Bub,et al.  Adiponectin as a growth inhibitor in prostate cancer cells. , 2006, Biochemical and biophysical research communications.

[122]  C. Mantzoros,et al.  Adiponectin signals in prostate cancer cells through Akt to activate the mammalian target of rapamycin pathway. , 2007, Endocrine-related cancer.

[123]  M. Szymańska,et al.  Expression of Leptin, Leptin Receptor, and Hypoxia‐Inducible Factor 1α in Human Endometrial Cancer , 2007, Annals of the New York Academy of Sciences.

[124]  A. Ray,et al.  Effects of leptin on human breast cancer cell lines in relationship to estrogen receptor and HER2 status. , 2007, International journal of oncology.

[125]  C. Friedenreich,et al.  Plasma adiponectin levels and endometrial cancer risk in pre- and postmenopausal women. , 2007, The Journal of clinical endocrinology and metabolism.

[126]  Y. Miyoshi,et al.  Demonstration of adiponectin receptors 1 and 2 mRNA expression in human breast cancer cells. , 2007, Cancer letters.

[127]  D. Rose,et al.  Adiposity, type 2 diabetes and the metabolic syndrome in breast cancer , 2007, Obesity reviews : an official journal of the International Association for the Study of Obesity.

[128]  C. Mantzoros,et al.  Total and high-molecular-weight adiponectin in breast cancer: in vitro and in vivo studies. , 2007, The Journal of clinical endocrinology and metabolism.