Adipoquinas y Cáncer

Estudios epidemiológicos han identificado que la obesidad es uno de los factores de riesgo para cáncer. En un estudio en el E.U.A. sobre 900. 000 adultos mostró una asociación entre un aumento del IMC y riesgo de muerte por cáncer en un período de 16 años63. Se acepta que la lesión se encuentra confinada a las células estromales y donde el medio ambiente de los adipocitos en mujeres obesas posmenopáusicas pueden estar comprometidos como en el cáncer de glándula mamaria y médula ósea. Experimentalmente se ha demostrado que los factores secretados por los adipocitos promueven la tumorogénesis incrementando la proliferación celular, potencial invasión, y angiogénesis. Es el caso de la proteína SP1 que en roedores promueve el desarrollo de líneas celulares para cáncer mamario64. Existe otra proteína de la matriz extracelular del adipocito que es muy abundante y se postula como regulatoria de la tumorogénesis y progresión del cáncer65. Faltan muchos estudios para conocer el papel que tienen los diferentes cofactores del adipocito en la genésis del cáncer.

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54. Kratchmarova I, Kalume DE, Blagoev B, et al. A proteomic approach for identification of secreted proteins during the differentiation of 3T3–L1 preadipocytes to adipocytes. Mol Cell Proteomics 2002; 1: 213-222.
55. Lin Y, Lee H, Berg AH, Lisanti MP, Shapiro L, Scherer PE. LPS activated TLR-4 receptor induces synthesis of the closely related receptor TLR-2 in adipocytes. J Biol Chem 2000; 275: 24255-24263.
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58. McIntosh M, Hausman R, Martin R, et al. Dehydroepiandrosterone attenuates preadipocyte growth in primary cultures of stromal vascular cells. Endocrinol Metab 1998; 38: E285-E293.
59. Steineger HH, Sorensen HN, Tugwood J, et al. Dexamethasone and insulin demonstrate marked and opposite regulation of the steadystate mRNA level of the PPAR in hepatic
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60. Wu Z, Bucher NLR, Farmer SR. Induction of PPAR during the conversion of 3T3 fibroblasts into adipocytes is mediated by CEBPß, CEBP and glucocorticoids. Mol Cell Biol 1996; 16: 4128-4136.
61. Smith PJ, Wise LS, Berkowitz R, et al. IGF1 is an essential regulator of the differentiation of 3T3L1 adipocytes. J Biol Chem 1998; 263:9402-9408[
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64. Howard BV. Lipoprotein metabolims in diabetes mellitus. J Lipid Res 1987; 28: 613- 628.
65. Weisweiler P. Plasma lipoprotein and lipase and lecithin: cholesterol acyltransferase activities in obese subjects before and after weigth reduction. J Clin Endocrinol Metab 1987; 65: 969-975.
39. Yamauchi T, Kamon J, Waki H, et al. Globular adiponectin protected ob/ob mice from diabetes and apoE deficient mice from atherosclerosis. J Biol Chem 2002; 278: 2461-2468.
40. Steppan CM, Bailey ST, Bhat S, Brown EJ, et al. The hormone resistin links obesity to diabetes. Nature 2001; 409: 307-312.
41. Pajvani UB, Du X, Combs TP, Berg AH, et al. Structure-function studies of the adipocyte secreted hormone Acrp30/adiponectin: implications for metabolic regulation and bioactivity. J Biol Chem 2002; 278: 9073-9085.
42. Faraj M, Havel PJ, Phelis S, et al. Plasma acylation-stimulating protein adiponectin, leptin, and ghrelin before and after weight loss induced by gastric bypass surgery in morbidly obese subjects. J Clin Endocrinol Metab 2003; 88: 1594-1602.
43. Fernández-Real JM, Broch M, Ricart W, et al. Plasma levels of the soluble fraction of Tumor Necrosis Factor Receptor -2 and insulin resistance. Diabetes 1998; 47: 1752- 1762.
44. Bluher M, Kratsch J, Praschke R. Plasma levels of tumor necrosis factor-α, angiotensin- II, growth hormone, and IGF-1 are not elevated in insulin-resistant obese individuals with impaired glucose tolerance. Diabetes Care 2001; 24: 328-334.
45. Xu H, Hirosumi J, Uysal T, Guler AD, Hotamisligil GS. Exclusive action of transmembrane TNF-α in adipose tissue leads to reduced adipose mass and local but not systemic insulin resistance. Endocrinology 2002; 143: 1502-1511.
46. Grunfeld C, Feingold KR. Role of cytokines in inducing hyperlipidemia. Diabetes Care 1992; 41: 97-101.
47. Fernández-Real JM, Vayreda M, Richart C, et al. Circulating IL-6 levels, blood pressure and insulin sensitivity in apparently healthy men and women. J Clin Endocrinol Metab 2001; 86: 1154-1159.
48. Päth G, Bornstein SR, Ehrart-Bornstein M, Scherbaum WA. Interleukin-6 and the interleukin-6 receptor in the human adrenal gland: expresión and effects on steroidogenesis. J Clin Endocrinol Metab 1997; 82: 2343-2349.
49. Kern Pa, Ranganathan S, Li C, Wood L, Ranganathan G. Adipose tissue tumor necrosis factor and IL-6 expression in human obesity and insulin resistance. Am J Physiol Endocrinol Metab 2001; 280: E745-E751.
50. Pradhan AD, Manson JE, Rifai N, et al. Creactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA 2001; 286: 327-334.
51. Humphries SE, Luong LA, Ogg MS, et al. The interleukin-6-174 G/C promoter polymorphism is associated with risk of coronary heart disease and systolic blood pressure in helthy men. Eur Heart J 2001; 22: 2243-2252.
52. Ouchi N, Kihara S, Arita Y, et al. Novel modulator of endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin. Circulation 1999; 100: 2473-2476.
53. Ouchi N, Kihara S, Arita Y, et al. Adiponectin, an adipocyte-derived plasma protein, inhibits NF-kb signalling through a cAMP-dependent pathway. Circulation 2000; 102: 1296- 1301.
54. Kratchmarova I, Kalume DE, Blagoev B, et al. A proteomic approach for identification of secreted proteins during the differentiation of 3T3–L1 preadipocytes to adipocytes. Mol Cell Proteomics 2002; 1: 213-222.
55. Lin Y, Lee H, Berg AH, Lisanti MP, Shapiro L, Scherer PE. LPS activated TLR-4 receptor induces synthesis of the closely related receptor TLR-2 in adipocytes. J Biol Chem 2000; 275: 24255-24263.
56. Mick GJ, Wang X, McCormick K. White adipocyte vascular endothelial growth factor: regulation by insulin. Endocrinology 2002; 143: 948-953.
57. Benito M, Valverde AM, Lorenzo M. IGF1: a mitogen involved in differentiation processes in mammalian cells. Int J Biochem Cell Biol 1996; 28: 499-510.
58. McIntosh M, Hausman R, Martin R, et al. Dehydroepiandrosterone attenuates preadipocyte growth in primary cultures of stromal vascular cells. Endocrinol Metab 1998; 38: E285-E293.
59. Steineger HH, Sorensen HN, Tugwood J, et al. Dexamethasone and insulin demonstrate marked and opposite regulation of the steadystate mRNA level of the PPAR in hepatic
cells. Eur J Biochem 1994; 225: 967-974.
60. Wu Z, Bucher NLR, Farmer SR. Induction of PPAR during the conversion of 3T3 fibroblasts into adipocytes is mediated by CEBPß, CEBP and glucocorticoids. Mol Cell Biol 1996; 16: 4128-4136.
61. Smith PJ, Wise LS, Berkowitz R, et al. IGF1 is an essential regulator of the differentiation of 3T3L1 adipocytes. J Biol Chem 1998; 263:9402-9408[
62. Notelovitz M, Gudat JL, Ware MD, et al. Lipids and lipoproteins in women after oophorectomy and the response to estrogen therapy. Br J Obstet Gynaecol. 1983; 90: 171-177.
63. Commingus SR. Benefics and risk of longterm postmenopausal hormone therapy. In cardiovascular disease and HRT. Edit Samside G. Parthenon Publi Group 9. 1991.
64. Howard BV. Lipoprotein metabolims in diabetes mellitus. J Lipid Res 1987; 28: 613- 628.
65. Weisweiler P. Plasma lipoprotein and lipase and lecithin: cholesterol acyltransferase activities in obese subjects before and after weigth reduction. J Clin Endocrinol Metab 1987; 65: 969-975.