Obesity, diabetes and metabolic syndrome impact on tumor angiogenesis

Tumor Angiogenesis Regulators

Volumn , Issue , 2013, Pages 411-432

  Incio, João ^a   Soares, Raquel ^b  

^a MASSACHUSETTS GENERAL HOSPITAL   (United States)

^b University of Porto   (Portugal)

Author keywords

Adipokines; Angiogenesis; Cancer; Diabetes; Inflammation; Metabolic syndrome; Obesity

Indexed keywords

EID: 84939843259     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1201/b14842     Document Type: Chapter

References (98)

1. Anisimov, V. N., L. M. Berstein, P. A. Egormin, T. S. Piskunova, I. G. Popovich, M. A. Zabezhinski, I. G. Kovalenko, T. E. Poroshina, A. V. Semenchenko, M. Provinciali, F. Re and C. Franceschi (2005). “Effect of metformin on life span and on the development of spontaneous mammary tumors in HER-2/neu transgenic mice.” Exp Gerontol 40(8-9): 685-693.
2. Artac, M. and K. Altundag (2012). “Leptin and breast cancer: an overview.” Med Oncol 29(3): 1510-1514.
3. Bianchini, F., R. Kaaks and H. Vainio (2002). “Overweight, obesity, and cancer risk.” Lancet Oncol 3(9): 565-574.
4. Bouloumie, A., K. Lolmede, C. Sengenes, J. Galitzky and M. Lafontan (2002). “Angiogenesis in adipose tissue.” Ann Endocrinol (Paris) 63(2 Pt 1): 91-95.
5. Boyd, D. B. (2003). “Insulin and cancer.” Integr Cancer Ther 2(4): 315-329.
6. Brakenhielm, E., R. Cao, B. Gao, B. Angelin, B. Cannon, P. Parini and Y. Cao (2004a). “Angiogenesis inhibitor, TNP-470, prevents diet-induced and genetic obesity in mice.” Circ Res 94(12): 1579-1588.
7. Burke, A. P., F. D. Kolodgie, A. Zieske, D. R. Fowler, D. K. Weber, P. J. Varghese, A. Farb and R. Virmani (2004). “Morphologic findings of coronary atherosclerotic plaques in diabetics: a postmortem study.” Arterioscler Thromb Vasc Biol 24(7): 1266-1271.
8. Calle, E. E. and R. Kaaks (2004a). “Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms.” Nat Rev Cancer 4(8): 579-591.
9. Calle, E. E., C. Rodriguez, K. Walker-Thurmond and M. J. Thun (2003). “Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults.” N Engl J Med 348(17): 1625-1638.
10. Calle, E. E. and M. J. Thun (2004b). “Obesity and cancer.” Oncogene 23(38): 6365-6378.
11. Cao, R., E. Brakenhielm, C. Wahlestedt, J. Thyberg and Y. Cao (2001). “Leptin induces vascular permeability and synergistically stimulates angiogenesis with FGF-2 and VEGF.” Proc Natl Acad Sci USA 98(11): 6390-6395.
12. Carmeliet, P. and R. K. Jain (2011a). “Molecular mechanisms and clinical applications of angiogenesis.” Nature 473(7347): 298-307.
13. Carmeliet, P. and R. K. Jain (2011b). “Principles and mechanisms of vessel normalization for cancer and other angiogenic diseases.” Nat Rev Drug Discov 10(6): 417-427.
14. Catalan, V., J. Gomez-Ambrosi, A. Rodriguez, B. Ramirez, C. Silva, F. Rotellar, J. L. Hernandez-Lizoain, J. Baixauli, V. Valenti, F. Pardo, J. Salvador and G. Fruhbeck (2011). “Up-regulation of the novel proinflammatory adipokines lipocalin-2, chitinase-3 like-1 and osteopontin as well as angiogenic-related factors in visceral adipose tissue of patients with colon cancer.” J Nutr Biochem 22(7): 634-641.
15. CDC (2007). “Centers for Disease Control and Prevention, National Diabetes Surveillance System: prevalence of diabetes.” Version current 6 October 2005 nternet: http://www.cdc.gov/diabetes/statistics/prev/national/figpersons.htm
16. Cho, C. H., Y. J. Koh, J. Han, H. K. Sung, H. Jong Lee, T. Morisada, R. A. Schwendener, R. A. Brekken, G. Kang, Y. Oike, T. S. Choi, T. Suda, O. J. Yoo and G. Y. Koh (2007). “Angiogenic role of LYVE-1-positive macrophages in adipose tissue.” Circ Res 100(4): e47-57.
17. Costa, C., J. Incio and R. Soares (2007). “Angiogenesis and chronic inflammation: cause or consequence?" Angiogenesis 10(3): 149-166.
18. Costa, C., R. Soares and F. Schmitt (2004). “Angiogenesis: now and then.” APMIS 112(7-8): 402-412.
19. Creager, M. A., T. F. Luscher, F. Cosentino and J. A. Beckman (2003). “Diabetes and vascular disease: pathophysiology, clinical consequences, and medical therapy: Part I.” Circulation 108(12): 1527-1532.
20. Daling, J. R., K. E. Malone, D. R. Doody, L. G. Johnson, J. R. Gralow and P. L. Porter (2001). “Relation of body mass index to tumor markers and survival among young women with invasive ductal breast carcinoma.” Cancer 92(4): 720-729.
21. Delafontaine, P., Y. H. Song and Y. Li (2004). “Expression, regulation, and function of IGF-1, IGF-1R, and IGF-1 binding proteins in blood vessels.” Arterioscler Thromb Vasc Biol 24(3): 435-444.
22. Dogan, S., X. Hu, Y. Zhang, N. J. Maihle, J. P. Grande and M. P. Cleary (2007). “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 9(6): R91.
23. Duraisamy, Y., M. Slevin, N. Smith, J. Bailey, J. Zweit, C. Smith, N. Ahmed and J. Gaffney (2001). “Effect of glycation on basic fibroblast growth factor induced angiogenesis and activation of associated signal transduction pathways in vascular endothelial cells: possible relevance to wound healing in diabetes.” Angiogenesis 4(4): 277-288.
24. Eliassen, A. H., G. A. Colditz, B. Rosner, W. C. Willett and S. E. Hankinson (2006). “Adult weight change and risk of postmenopausal breast cancer.” JAMA 296(2): 193-201.
25. Fain, J. N. (2006). “Release of interleukins and other inflammatory cytokines by human adipose tissue is enhanced in obesity and primarily due to the nonfat cells.” Vitam Horm 74: 443-477.
26. Fischer, S., M. Hanefeld, S. M. Haffner, C. Fusch, U. Schwanebeck, C. Kohler, K. Fucker and U. Julius (2002). “Insulin-resistant patients with type 2 diabetes mellitus have higher serum leptin levels independently of body fat mass.” Acta Diabetol 39(3): 105-110.
27. Flegal, K. M., M. D. Carroll, C. L. Ogden and C. L. Johnson (2002). “Prevalence and trends in obesity among US adults, 1999-2000.” JAMA 288(14): 1723-1727.
28. Fox, C. S., M. J. Pencina, J. B. Meigs, R. S. Vasan, Y. S. Levitzky and R. B. D’Agostino, Sr. (2006). “Trends in the incidence of type 2 diabetes mellitus from the 1970s to the 1990s: the Framingham Heart Study.” Circulation 113(25): 2914-2918.
29. Fukumura, D., A. Ushiyama, D. G. Duda, L. Xu, J. Tam, V. Krishna, K. Chatterjee, I. Garkavtsev and R. K. Jain (2003). “Paracrine regulation of angiogenesis and adipocyte differentiation during in vivo adipogenesis.” Circ Res 93(9): e88-97.
30. Furundzija, V., J. Fritzsche, J. Kaufmann, H. Meyborg, E. Fleck, K. Kappert and P. Stawowy (2010). “IGF-1 increases macrophage motility via PKC/p38-dependent alphavbeta3-integrin inside-out signaling.” Biochem Biophys Res Commun 394(3): 786-791.
31. Gallagher, E. J. and D. LeRoith (2010). “The proliferating role of insulin and insulinlike growth factors in cancer.” Trends Endocrinol Metab 21(10): 610-618.
32. Godsland, I. F. (2009). “Insulin resistance and hyperinsulinaemia in the development and progression of cancer.” Clin Sci (Lond) 118(5): 315-332.
33. Gonzalez, R. R., S. Cherfils, M. Escobar, J. H. Yoo, C. Carino, A. K. Styer, B. T. Sullivan, H. Sakamoto, A. Olawaiye, T. Serikawa, M. P. Lynch and B. R. Rueda (2006). “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 281(36): 26320-26328.
34. Goodwin, P. J. and V. Stambolic (2011). “Obesity and insulin resistance in breast cancer - Chemoprevention strategies with a focus on metformin.” Breast 20 Suppl 3: S31-35.
35. Gordon, R. R., K. W. Hunter, P. Sorensen and D. Pomp (2008). “Genotype X diet interactions in mice predisposed to mammary cancer. I. Body weight and fat.” Mamm Genome 19(3): 163-178.
36. Gruen, M. L., M. Hao, D. W. Piston and A. H. Hasty (2007). “Leptin requires canonical migratory signaling pathways for induction of monocyte and macrophage chemotaxis.” Am J Physiol Cell Physiol 293(5): C1481-1488.
37. Gu, J. W., E. Young, S. G. Patterson, K. L. Makey, J. Wells, M. Huang, K. B. Tucker and L. Miele (2011). “Postmenopausal obesity promotes tumor angiogenesis and breast cancer progression in mice.” Cancer Biol Ther 11(10): 910-917.
38. Guiu, B., J. M. Petit, F. Bonnetain, S. Ladoire, S. Guiu, J. P. Cercueil, D. Krause, P. Hillon, C. Borg, B. Chauffert and F. Ghiringhelli (2010). “Visceral fat area is an independent predictive biomarker of outcome after first-line bevacizumab-based treatment in metastatic colorectal cancer.” Gut 59(3): 341-347.
39. Hagendoorn, J., R. Tong, D. Fukumura, Q. Lin, J. Lobo, T. P. Padera, L. Xu, R. Kucherlapati and R. K. Jain (2006). “Onset of abnormal blood and lymphatic vessel function and interstitial hypertension in early stages of carcinogenesis.” Cancer Res 66(7): 3360-3364.
40. Haydon, A. M., R. J. Macinnis, D. R. English and G. G. Giles (2006). “Effect of physical activity and body size on survival after diagnosis with colorectal cancer.” Gut 55(1): 62-67.
41. Hosogai, N., A. Fukuhara, K. Oshima, Y. Miyata, S. Tanaka, K. Segawa, S. Furukawa, Y. Tochino, R. Komuro, M. Matsuda and I. Shimomura (2007). “Adipose tissue hypoxia in obesity and its impact on adipocytokine dysregulation.” Diabetes 56(4): 901-911.
42. Ibrahim, M. M. (2010). “Subcutaneous and visceral adipose tissue: structural and functional differences.” Obes Rev 11(1): 11-18.
43. Incio, J., R. Lopes, I. Azevedo and S. Soares (2006). “Prevention of both angio and atherogenesis: inhibitory properties of polyphenols (Xanthumol) in smooth muscle cells.” European Journal of Medical Research 11: 122(Suppl II).
44. Isoda, K., J. L. Young, A. Zirlik, L. A. MacFarlane, N. Tsuboi, N. Gerdes, U. Schonbeck and P. Libby (2006). “Metformin inhibits proinflammatory responses and nuclear factor-kappaB in human vascular wall cells.” Arterioscler Thromb Vasc Biol 26(3): 611-617.
45. Khalid, S., D. Hwang, Y. Babichev, R. Kolli, S. Altamentova, S. Koren, P. J. Goodwin, M. Ennis, M. Pollak, N. Sonenberg and I. G. Fantus (2009). “Evidence for a tumor promoting effect of high-fat diet independent of insulin resistance in HER2/Neu mammary carcinogenesis.” Breast Cancer Res Treat 122(3): 647-659.
46. Kim, P., E. Chung, H. Yamashita, K. E. Hung, A. Mizoguchi, R. Kucherlapati, D. Fukumura, R. K. Jain and S. H. Yun (2010). “In vivo wide-area cellular imaging by side-view endomicroscopy.” Nat Methods 7(4): 303-305.
47. Kimura, Y. and M. Sumiyoshi (2007). “High-fat, high-sucrose, and high-cholesterol diets accelerate tumor growth and metastasis in tumor-bearing mice.” Nutr Cancer 59(2): 207-216.
48. Kobayashi, H., N. Ouchi, S. Kihara, K. Walsh, M. Kumada, Y. Abe, T. Funahashi and Y. Matsuzawa (2004). “Selective suppression of endothelial cell apoptosis by the high molecular weight form of adiponectin.” Circ Res 94(4): e27-31.
49. Ladoire, S., F. Bonnetain, M. Gauthier, S. Zanetta, J. M. Petit, S. Guiu, I. Kermarrec, E. Mourey, F. Michel, D. Krause, P. Hillon, L. Cormier, F. Ghiringhelli and B. Guiu (2011). “Visceral fat area as a new independent predictive factor of survival in patients with metastatic renal cell carcinoma treated with antiangiogenic agents.” Oncologist 16(1): 71-81.
50. Llaverias, G., C. Danilo, Y. Wang, A. K. Witkiewicz, K. Daumer, M. P. Lisanti and P. G. Frank (2010). “A Western-type diet accelerates tumor progression in an autochthonous mouse model of prostate cancer.” Am J Pathol 177(6): 3180-3191.
51. Lolmede, K., V. Durand de Saint Front, J. Galitzky, M. Lafontan and A. Bouloumie (2003). “Effects of hypoxia on the expression of proangiogenic factors in differentiated 3T3-F442A adipocytes.” Int J Obes Relat Metab Disord 27(10): 1187-1195.
52. Lysaght, J., E. P. van der Stok, E. H. Allott, R. Casey, C. L. Donohoe, J. M. Howard, S. A. McGarrigle, N. Ravi, J. V. Reynolds and G. P. Pidgeon (2011). “Proinflammatory and tumour proliferative properties of excess visceral adipose tissue.” Cancer Lett 312(1): 62-72.
53. Maccio, A., C. Madeddu, G. Gramignano, C. Mulas, C. Floris, D. Massa, G. Astara, P. Chessa and G. Mantovani (2010). “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.” J Mol Med (Berl) 88(7): 677-686.
54. Majed, B., T. Moreau, K. Senouci, R. m. Salmon, A. Fourquet and B. Asselain (2008). “Is obesity an independent prognosis factor in woman breast cancer?" Breast Cancer Research and Treatment 111(2): 329-342.
55. Martin, M., R. Hayward, A. Viros and R. Marais (2012). “Metformin Accelerates the Growth of BRAFV600E -Driven Melanoma by Upregulating VEGF-A.” Cancer Discovery 2: 344-355.
56. Matsuzawa, Y. (2006). “Therapy Insight: adipocytokines in metabolic syndrome and related cardiovascular disease.” Nat Clin Pract Cardiovasc Med 3(1): 35-42.
57. Meyerhardt, J. A., D. Niedzwiecki, D. Hollis, L. B. Saltz, R. J. Mayer, H. Nelson, R. Whittom, A. Hantel, J. Thomas and C. S. Fuchs (2008). “Impact of body mass index and weight change after treatment on cancer recurrence and survival in patients with stage III colon cancer: findings from Cancer and Leukemia Group B 89803.” J Clin Oncol 26(25): 4109-4115.
58. Mokdad, A. H., J. S. Marks, D. F. Stroup and J. L. Gerberding (2004). “Actual causes of death in the United States, 2000.” Jama 291(10): 1238-1245.
59. Monteiro, R., R. Soares, S. Guerreiro, D. Pestana, C. Calhau and I. Azevedo (2009). “Red wine increases adipose tissue aromatase expression and regulates body weight and adipocyte size.” Nutrition 25(6): 699-705.
60. Moses, A. G., N. Dowidar, B. Holloway, I. Waddell, K. C. Fearon and J. A. Ross (2001). “Leptin and its relation to weight loss, ob gene expression and the acutephase response in surgical patients.” Br J Surg 88(4): 588-593.
61. Murphy, L. J., P. Molnar, X. Lu and H. Huang (1995). “Expression of human insulinlike growth factor-binding protein-3 in transgenic mice.” J Mol Endocrinol 15(3): 293-303.
62. Negrao, M. R., J. Incio, R. Lopes, I. Azevedo and R. Scares (2007). “Xanthohumol inhibits angiogenic vessels but not stable vessels.” Faseb Journal 21(6): A1095-A1095.
63. Nunez, N. P., W. J. Oh, J. Rozenberg, C. Perella, M. Anver, J. C. Barrett, S. N. Perkins, D. Berrigan, J. Moitra, L. Varticovski, S. D. Hursting and C. Vinson (2006). “Accelerated tumor formation in a fatless mouse with type 2 diabetes and inflammation.” Cancer Res 66(10): 5469-5476.
64. Nunez, N. P., S. N. Perkins, N. C. Smith, D. Berrigan, D. M. Berendes, L. Varticovski, J. C. Barrett and S. D. Hursting (2008). “Obesity accelerates mouse mammary tumor growth in the absence of ovarian hormones.” Nutr Cancer 60(4): 534-541.
65. Olshansky, S. J., D. J. Passaro, R. C. Hershow, J. Layden, B. A. Carnes, J. Brody, L. Hayflick, R. N. Butler, D. B. Allison and D. S. Ludwig (2005). “A potential decline in life expectancy in the United States in the 21st century.” N Engl J Med 352(11): 1138-1145.
66. Ouchi, N., H. Kobayashi, S. Kihara, M. Kumada, K. Sato, T. Inoue, T. Funahashi and K. Walsh (2004). “Adiponectin stimulates angiogenesis by promoting cross-talk between AMP-activated protein kinase and Akt signaling in endothelial cells.” J Biol Chem 279(2): 1304-1309.
67. Paoletti, R., C. Bolego, A. Poli and A. Cignarella (2006). “Metabolic syndrome, inflammation and atherosclerosis.” Vasc Health Risk Manag 2(2): 145-152.
68. Park, J., D. M. Euhus and P. E. Scherer (2011). “Paracrine and endocrine effects of adipose tissue on cancer development and progression.” Endocr Rev 32(4): 550-570.
69. Peeters, A., J. J. Barendregt, F. Willekens, J. P. Mackenbach, A. Al Mamun and L. Bonneux (2003). “Obesity in adulthood and its consequences for life expectancy: a life-table analysis.” Ann Intern Med 138(1): 24-32.
70. Phoenix, K. N., F. Vumbaca and K. P. Claffey (2009). “Therapeutic metformin/AMPK activation promotes the angiogenic phenotype in the ERalpha negative MDA-MB-435 breast cancer model.” Breast Cancer Res Treat 113(1): 101-111.
71. Pischon, T., P. H. Lahmann, H. Boeing, C. Friedenreich, T. Norat, A. Tjonneland, J. Halkjaer, K. Overvad, F. Clavel-Chapelon, M. C. Boutron-Ruault, G. Guernec, M. M. Bergmann, J. Linseisen, N. Becker, A. Trichopoulou, D. Trichopoulos, S. Sieri, D. Palli, R. Tumino, P. Vineis, S. Panico, P. H. Peeters, H. B. Bueno-de-Mesquita, H. C. Boshuizen, B. Van Guelpen, R. Palmqvist, G. Berglund, C. A. Gonzalez, M. Dorronsoro, A. Barricarte, C. Navarro, C. Martinez, J. R. Quiros, A. Roddam, N. Allen, S. Bingham, K. T. Khaw, P. Ferrari, R. Kaaks, N. Slimani and E. Riboli (2006). “Body size and risk of colon and rectal cancer in the European Prospective Investigation Into Cancer and Nutrition (EPIC).” J Natl Cancer Inst 98(13): 920-931.
72. Polverini, P. J. and S. J. Leibovich (1984). “Induction of neovascularization in vivo and endothelial proliferation in vitro by tumor-associated macrophages.” Lab Invest 51(6): 635-642.
73. Protani, M., M. Coory and J. H. Martin (2010). “Effect of obesity on survival of women with breast cancer: systematic review and meta-analysis.” Breast Cancer Res Treat 123(3): 627-635.
74. Rausch, M. E., S. Weisberg, P. Vardhana and D. V. Tortoriello (2008). “Obesity in C57BL/6J mice is characterized by adipose tissue hypoxia and cytotoxic T-cell infiltration.” Int J Obes (Lond) 32(3): 451-463.
75. Reinmuth, N., W. Liu, F. Fan, Y. D. Jung, S. A. Ahmad, O. Stoeltzing, C. D. Bucana, R. Radinsky and L. M. Ellis (2002). “Blockade of insulin-like growth factor I receptor function inhibits growth and angiogenesis of colon cancer.” Clin Cancer Res 8(10): 3259-3269.
76. Rose, D. P., J. M. Connolly and C. L. Meschter (1991). “Effect of dietary fat on human breast cancer growth and lung metastasis in nude mice.” J Natl Cancer Inst 83(20): 1491-1495.
77. Rose, D. P., D. Komninou and G. D. Stephenson (2004). “Obesity, adipocytokines, and insulin resistance in breast cancer.” Obes Rev 5(3): 153-165.
78. Rupnick, M. A., D. Panigrahy, C. Y. Zhang, S. M. Dallabrida, B. B. Lowell, R. Langer and M. J. Folkman (2002). “Adipose tissue mass can be regulated through the vasculature.” Proc Natl Acad Sci USA 99(16): 10730-10735.
79. Ryan, P. D. and P. E. Goss (2008). “The emerging role of the insulin-like growth factor pathway as a therapeutic target in cancer.” Oncologist 13(1): 16-24.
80. Sengupta, N., A. Afzal, S. Caballero, K. H. Chang, L. C. Shaw, J. J. Pang, V. C. Bond, I. Bhutto, T. Baba, G. A. Lutty and M. B. Grant (2010). “Paracrine modulation of CXCR4 by IGF-1 and VEGF: implications for choroidal neovascularization.” Invest Ophthalmol Vis Sci 51(5): 2697-2704.
81. Shojaei, F., X. Wu, A. K. Malik, C. Zhong, M. E. Baldwin, S. Schanz, G. Fuh, H. P. Gerber and N. Ferrara (2007). “Tumor refractoriness to anti-VEGF treatment is mediated by CD11b+Gr1+ myeloid cells.” Nat Biotechnol 25(8): 911-920.
82. Sierra-Honigmann, M. R., A. K. Nath, C. Murakami, G. Garcia-Cardena, A. Papapetropoulos, W. C. Sessa, L. A. Madge, J. S. Schechner, M. B. Schwabb, P. J. Polverini and J. R. Flores-Riveros (1998). “Biological action of leptin as an angiogenic factor.” Science 281(5383): 1683-1686.
83. Smith, L. E., W. Shen, C. Perruzzi, S. Soker, F. Kinose, X. Xu, G. Robinson, S. Driver, J. Bischoff, B. Zhang, J. M. Schaeffer and D. R. Senger (1999). “Regulation of vascular endothelial growth factor-dependent retinal neovascularization by insulin-like growth factor-1 receptor.” Nat Med 5(12): 1390-1395.
84. Soares, R. and C. Costa (2009). “Angiogenesis in metabolic syndrome (book chapter).” Oxidative stress, inflammation and angiogenesis in metabolic syndrome (Springer-Verlag, The Netherlands): 85-99.
85. Steffens, S., V. Grunwald, K. I. Ringe, C. Seidel, H. Eggers, M. Schrader, F. Wacker, M. A. Kuczyk and A. J. Schrader (2011). “Does obesity influence the prognosis of metastatic renal cell carcinoma in patients treated with vascular endothelial growth factor-targeted therapy?" Oncologist 16(11): 1565-1571.
86. Suganami, E., H. Takagi, H. Ohashi, K. Suzuma, I. Suzuma, H. Oh, D. Watanabe, T. Ojima, T. Suganami, Y. Fujio, K. Nakao, Y. Ogawa and N. Yoshimura (2004). “Leptin stimulates ischemia-induced retinal neovascularization: possible role of vascular endothelial growth factor expressed in retinal endothelial cells.” Diabetes 53(9): 2443-2448.
87. Tam, J., D. G. Duda, J. Y. Perentes, R. S. Quadri, D. Fukumura and R. K. Jain (2009). “Blockade of VEGFR2 and not VEGFR1 can limit diet-induced fat tissue expansion: role of local versus bone marrow-derived endothelial cells.” PLoS One 4(3): e4974.
88. Uzzan, B., P. Nicolas, M. Cucherat and G. Y. Perret (2004). “Microvessel density as a prognostic factor in women with breast cancer: a systematic review of the literature and meta-analysis.” Cancer Res 64(9): 2941-2955.
89. Volkova, E., J. A. Willis, J. E. Wells, B. A. Robinson, G. U. Dachs and M. J. Currie (2011). “Association of angiopoietin-2, C-reactive protein and markers of obesity and insulin resistance with survival outcome in colorectal cancer.” Br J Cancer 104(1): 51-59.
90. Vona-Davis, L., M. Howard-McNatt and D. P. Rose (2007). “Adiposity, type 2 diabetes and the metabolic syndrome in breast cancer.” Obes Rev 8(5): 395-408.
91. Wang, B., I. S. Wood and P. Trayhurn (2007). “Dysregulation of the expression and secretion of inflammation-related adipokines by hypoxia in human adipocytes.” Pflugers Arch 455(3): 479-492.
92. Weisberg, S. P., D. McCann, M. Desai, M. Rosenbaum, R. L. Leibel and A. W. Ferrante, Jr. (2003). “Obesity is associated with macrophage accumulation in adipose tissue.” J Clin Invest 112(12): 1796-1808.
93. Wu, Y., P. Brodt, H. Sun, W. Mejia, R. Novosyadlyy, N. Nunez, X. Chen, A. Mendoza, S. H. Hong, C. Khanna and S. Yakar (2010). “Insulin-like growth factor-I regulates the liver microenvironment in obese mice and promotes liver metastasis.” Cancer Res 70(1): 57-67.
94. Wu, Y., S. Yakar, L. Zhao, L. Hennighausen and D. LeRoith (2002). “Circulating insulin-like growth factor-I levels regulate colon cancer growth and metastasis.” Cancer Res 62(4): 1030-1035.
95. Xu, H., G. T. Barnes, Q. Yang, G. Tan, D. Yang, C. J. Chou, J. Sole, A. Nichols, J. S. Ross, L. A. Tartaglia and H. Chen (2003). “Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance.” J Clin Invest 112(12): 1821-1830.
96. Xue, F. and K. B. Michels (2007). “Diabetes, metabolic syndrome, and breast cancer: a review of the current evidence.” Am J Clin Nutr 86(3): s823-835.
97. Yang, H., B. Nan, S. Yan, M. Li, Q. Yao and C. Chen (2005). “C-reactive protein decreases expression of VEGF receptors and neuropilins and inhibits VEGF165-induced cell proliferation in human endothelial cells.” Biochem Biophys Res Commun 333(3): 1003-1010.
98. Zimmet, P. Z., D. J. McCarty and M. P. de Courten (1997). “The global epidemiology of non-insulin-dependent diabetes mellitus and the metabolic syndrome.” J Diabetes Complications 11(2): 60-68.