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Journal of Mammary Gland Biology and Neoplasia
Published in: Journal of Mammary Gland Biology and Neoplasia 3-4/2013

01-12-2013

The Obesity-Inflammation-Eicosanoid Axis in Breast Cancer

Authors: Linda Vona-Davis, David P. Rose

Published in: Journal of Mammary Gland Biology and Neoplasia | Issue 3-4/2013

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Abstract

Inflammation of the adipose tissues occurs in association with obesity. This inflammatory process leads to the induction of cyclooxygenase-2 (COX-2) expression and a consequent elevation in prostaglandin (PG) production, which, together with proinflammatory cytokines, induce aromatase expression and estrogen synthesis. Infiltrating macrophages support the growth of breast epithelial cells and vascular endothelial cells by producing a milieu of cytokines and growth factors. This scenario creates a microenvironment favorable to breast cancer growth and invasion. The eicosanoids promote further development and growth of breast cancers indirectly by the induction of aromatase, particularly in estrogen positive breast cancers, or by direct stimulatory effect of PGE2 and lipoxygenase (LOX) products on the more aggressive, estrogen-independent tumors. Beyond this, the local production of estrogens and proinflammatory cytokines which occurs in association with breast adipose tissue inflammation, and consequent activation of the estrogen receptor and nuclear factor-κB, provides a mechanism by which breast cancers develop resistance to selective estrogen receptor modulation and aromatase inhibitor therapy. The obesity-inflammation-eicosanoid axis in breast cancer does offer a therapeutic target for the prevention of relapse in breast cancer by improving the efficacy of antiaromatase therapy using COX/LOX inhibitors; however, careful consideration of menopausal status and obesity in patients is warranted.
Literature
1.
Harvie M, Hooper L, Howell AH. Central obesity and breast cancer risk: a systematic review. Obes Rev. 2003;4:157–73.PubMed
2.
Stephenson GD, Rose DP. Breast cancer and obesity: an update. Nutr Cancer. 2003;45:1–16.PubMed
3.
Rose DP, Vona-Davis L. Interaction between menopausal status and obesity in affecting breast cancer risk. Maturitas. 2010;66:33–8.PubMed
4.
Maccio A, Madeddu C. Obesity, inflammation, and postmenopausal breast cancer: therapeutic implications. Sci World J. 2011;11:2020–36.
5.
Amadou A, Ferrari P, Muwonge R, et al. Overweight, obesity and risk of premenopausal breast cancer according to ethnicity: a systematic review and dose-response meta-analysis. Obes Rev. 2013.
6.
Suzuki R, Orsini N, Saji S, Key TJ, Wolk A. Body weight and incidence of breast cancer defined by estrogen and progesterone receptor status—a meta-analysis. Int J Cancer. 2009;124:698–712.PubMed
7.
Cotterchio M, Kreiger N, Theis B, Sloan M, Bahl S. Hormonal factors and the risk of breast cancer according to estrogen- and progesterone-receptor subgroup. Cancer Epidemiol Biomarkers Prev. 2003;12:1053–60.PubMed
8.
Niraula S, Ocana A, Ennis M, Goodwin PJ. Body size and breast cancer prognosis in relation to hormone receptor and menopausal status: a meta-analysis. Breast Cancer Res Treat. 2012;134:769–81.PubMed
9.
Subbaramaiah K, Howe LR, Bhardwaj P, et al. Obesity is associated with inflammation and elevated aromatase expression in the mouse mammary gland. Cancer Prev Res (Phila). 2011;4:329–46.
10.
Morris PG, Hudis CA, Giri D, et al. Inflammation and increased aromatase expression occur in the breast tissue of obese women with breast cancer. Cancer Prev Res (Phila). 2011;4:1021–9.
11.
Hsieh PS, Jin JS, Chiang CF, Chan PC, Chen CH, Shih KC. COX-2-mediated inflammation in fat is crucial for obesity-linked insulin resistance and fatty liver. Obesity (Silver Spring). 2009;17:1150–7.
12.
Subbaramaiah K, Morris PG, Zhou XK, et al. Increased levels of COX-2 and prostaglandin E2 contribute to elevated aromatase expression in inflamed breast tissue of obese women. Cancer Discov. 2012;2:356–65.PubMed
13.
Chakrabarti SK, Wen Y, Dobrian AD, et al. Evidence for activation of inflammatory lipoxygenase pathways in visceral adipose tissue of obese Zucker rats. Am J Physiol Endocrinol Metab. 2011;300:E175–87.PubMed
14.
Flegal KM, Carroll MD, Kit BK, Ogden CL. Prevalence of obesity and trends in the distribution of body mass index among US adults, 1999–2010. JAMA. 2012;307:491–7.PubMed
15.
Rodriguez A, Catalan V, Gomez-Ambrosi J, Fruhbeck G. Visceral and subcutaneous adiposity: are both potential therapeutic targets for tackling the metabolic syndrome? Curr Pharm Des. 2007;13:2169–75.PubMed
16.
Alvehus M, Buren J, Sjostrom M, Goedecke J, Olsson T. The human visceral fat depot has a unique inflammatory profile. Obesity (Silver Spring). 2010;18:879–83.
17.
Bulun SE, Chen D, Moy I, Brooks DC, Zhao H. Aromatase, breast cancer and obesity: a complex interaction. Trends Endocrinol Metab. 2012;23:83–9.PubMed
18.
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.PubMed
19.
Friedenreich CM, Courneya KS, Bryant HE. Case-control study of anthropometric measures and breast cancer risk. Int J Cancer. 2002;99:445–52.PubMed
20.
Connolly BS, Barnett C, Vogt KN, Li T, Stone J, Boyd NF. A meta-analysis of published literature on waist-to-hip ratio and risk of breast cancer. Nutr Cancer. 2002;44:127–38.PubMed
21.
Huang Z, Willett WC, Colditz GA, et al. Waist circumference, waist:hip ratio, and risk of breast cancer in the Nurses’ Health Study. Am J Epidemiol. 1999;150:1316–24.PubMed
22.
Carmichael AR. Obesity and prognosis of breast cancer. Obes Rev. 2006;7:333–40.PubMed
23.
Protani M, Coory M, Martin JH. Effect of obesity on survival of women with breast cancer: systematic review and meta-analysis. Breast Cancer Res Treat. 2010;123:627–35.PubMed
24.
Kamineni A, Anderson ML, White E, et al. Body mass index, tumor characteristics, and prognosis following diagnosis of early-stage breast cancer in a mammographically screened population. Cancer Causes Control. 2013;24:305–12.PubMed
25.
Dignam JJ, Wieand K, Johnson KA, et al. Effects of obesity and race on prognosis in lymph node-negative, estrogen receptor-negative breast cancer. Breast Cancer Res Treat. 2006;97:245–54.PubMed
26.
Borugian MJ, Sheps SB, Kim-Sing C, et al. Waist-to-hip ratio and breast cancer mortality. Am J Epidemiol. 2003;158:963–8.PubMed
27.
Abrahamson PE, Gammon MD, Lund MJ, et al. General and abdominal obesity and survival among young women with breast cancer. Cancer Epidemiol Biomarkers Prev. 2006;15:1871–7.PubMed
28.
Esteva FJ, Hortobagyi GN. Prognostic molecular markers in early breast cancer. Breast Cancer Res. 2004;6:109–18.PubMed
29.
Cui X, Zhang P, Deng W, et al. Insulin-like growth factor-I inhibits progesterone receptor expression in breast cancer cells via the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin pathway: progesterone receptor as a potential indicator of growth factor activity in breast cancer. Mol Endocrinol. 2003;17:575–88.PubMed
30.
Cui X, Schiff R, Arpino G, Osborne CK, Lee AV. Biology of progesterone receptor loss in breast cancer and its implications for endocrine therapy. J Clin Oncol. 2005;23:7721–35.PubMed
31.
Banegas MP, Li CI. Breast cancer characteristics and outcomes among Hispanic Black and Hispanic White women. Breast Cancer Res Treat. 2012;134:1297–304.PubMed
32.
Colditz GA, Rosner BA, Chen WY, Holmes MD, Hankinson SE. Risk factors for breast cancer according to estrogen and progesterone receptor status. J Natl Cancer Inst. 2004;96:218–28.PubMed
33.
Huang WY, Newman B, Millikan RC, Schell MJ, Hulka BS, Moorman PG. Hormone-related factors and risk of breast cancer in relation to estrogen receptor and progesterone receptor status. Am J Epidemiol. 2000;151:703–14.PubMed
34.
Enger SM, Ross RK, Paganini-Hill A, Carpenter CL, Bernstein L. Body size, physical activity, and breast cancer hormone receptor status: results from two case-control studies. Cancer Epidemiol Biomarkers Prev. 2000;9:681–7.PubMed
35.
Rosenberg LU, Einarsdottir K, Friman EI, et al. Risk factors for hormone receptor-defined breast cancer in postmenopausal women. Cancer Epidemiol Biomarkers Prev. 2006;15:2482–8.PubMed
36.
Reis-Filho JS, Tutt AN. Triple negative tumours: a critical review. Histopathology. 2008;52:108–18.PubMed
37.
Morris GJ, Naidu S, Topham AK, et al. Differences in breast carcinoma characteristics in newly diagnosed African-American and Caucasian patients: a single-institution compilation compared with the National Cancer Institute’s Surveillance, Epidemiology, and End Results database. Cancer. 2007;110:876–84.PubMed
38.
Jack RH, Davies EA, Renshaw C, et al. Differences in breast cancer hormone receptor status in ethnic groups: a London population. Eur J Cancer. 2013;49:696–702.PubMed
39.
Pierobon M, Frankenfeld CL. Obesity as a risk factor for triple-negative breast cancers: a systematic review and meta-analysis. Breast Cancer Res Treat. 2013;137:307–14.PubMed
40.
Turkoz FP, Solak M, Petekkaya I, et al. Association between common risk factors and molecular subtypes in breast cancer patients. Breast. 2013;22:344–50.PubMed
41.
Vona-Davis L, Rose DP. The influence of socioeconomic disparities on breast cancer tumor biology and prognosis: a review. J Womens Health (Larchmt). 2009;18:883–93.
42.
Vona-Davis L, Rose DP, Hazard H, et al. Triple-negative breast cancer and obesity in a rural Appalachian population. Cancer Epidemiol Biomarkers Prev. 2008;17:3319–24.PubMed
43.
Setiawan VW, Monroe KR, Wilkens LR, Kolonel LN, Pike MC, Henderson BE. Breast cancer risk factors defined by estrogen and progesterone receptor status: the multiethnic cohort study. Am J Epidemiol. 2009;169:1251–9.PubMed
44.
Enger SM, Greif JM, Polikoff J, Press M. Body weight correlates with mortality in early-stage breast cancer. Arch Surg. 2004;139:954–8.PubMed
45.
Cleveland RJ, Eng SM, Abrahamson PE, et al. Weight gain prior to diagnosis and survival from breast cancer. Cancer Epidemiol Biomarkers Prev. 2007;16:1803–11.PubMed
46.
Pfeiler G, Konigsberg R, Fesl C, et al. Impact of body mass index on the efficacy of endocrine therapy in premenopausal patients with breast cancer: an analysis of the prospective ABCSG-12 trial. J Clin Oncol. 2011;29:2653–9.PubMed
47.
Pfeiler G, Stoger H, Dubsky P, et al. Efficacy of tamoxifen +/− aminoglutethimide in normal weight and overweight postmenopausal patients with hormone receptor-positive breast cancer: an analysis of 1509 patients of the ABCSG-06 trial. Br J Cancer. 2013;108:1408–14.PubMed
48.
Sparano JA, Wang M, Zhao F, et al. Obesity at diagnosis is associated with inferior outcomes in hormone receptor-positive operable breast cancer. Cancer. 2012;118:5937–46.PubMed
49.
Dawood S, Lei X, Litton JK, Buchholz TA, Hortobagyi GN, Gonzalez-Angulo AM. Impact of body mass index on survival outcome among women with early stage triple-negative breast cancer. Clin Breast Cancer. 2012;12:364–72.PubMed
50.
Maehle BO, Tretli S, Skjaerven R, Thorsen T. Premorbid body weight and its relations to primary tumour diameter in breast cancer patients; its dependence on estrogen and progesteron receptor status. Breast Cancer Res Treat. 2001;68:159–69.PubMed
51.
Daling JR, Malone KE, Doody DR, Johnson LG, Gralow JR, Porter PL. Relation of body mass index to tumor markers and survival among young women with invasive ductal breast carcinoma. Cancer. 2001;92:720–9.PubMed
52.
Markkula A, Bromee A, Henningson M, et al. Given breast cancer, does breast size matter? Data from a prospective breast cancer cohort. Cancer Causes Control. 2012;23:1307–16.PubMed
53.
Maehle BO, Tretli S, Thorsen T. The associations of obesity, lymph node status and prognosis in breast cancer patients: dependence on estrogen and progesterone receptor status. APMIS. 2004;112:349–57.PubMed
54.
Rose DP, Vona-Davis L. Influence of obesity on breast cancer receptor status and prognosis. Expert Rev Anticancer Ther. 2009;9:1091–101.PubMed
55.
de Azambuja E, Cardoso F, De Castro Jr G, et al. Ki-67 as prognostic marker in early breast cancer: a meta-analysis of published studies involving 12,155 patients. Br J Cancer. 2007;96:1504–13.PubMed
56.
Pinder SE, Ellis IO, Galea M, O’Rouke S, Blamey RW, Elston CW. Pathological prognostic factors in breast cancer. III. Vascular invasion: relationship with recurrence and survival in a large study with long-term follow-up. Histopathology. 1994;24:41–7.PubMed
57.
Westenend PJ, Meurs CJ, Damhuis RA. Tumour size and vascular invasion predict distant metastasis in stage I breast cancer. Grade distinguishes early and late metastasis. J Clin Pathol. 2005;58:196–201.PubMed
58.
Badwe RA, Fentiman IS, Millis RR, Gregory WM. Body weight and vascular invasion in post-menopausal women with breast cancer. Br J Cancer. 1997;75:910–3.PubMed
59.
Demirkan B, Alacacioglu A, Yilmaz U. Relation of body mass index (BMI) to disease free (DFS) and distant disease free survivals (DDFS) among Turkish women with operable breast carcinoma. Jpn J Clin Oncol. 2007;37:256–65.PubMed
60.
Gillespie EF, Sorbero ME, Hanauer DA, et al. Obesity and angiolymphatic invasion in primary breast cancer. Ann Surg Oncol. 2010;17:752–9.PubMed
61.
Biglia N, Peano E, Sgandurra P, et al. Body mass index (BMI) and breast cancer: impact on tumor histopatologic features, cancer subtypes and recurrence rate in pre and postmenopausal women. Gynecol Endocrinol. 2013;29:263–7.PubMed
62.
Loi S, Milne RL, Friedlander ML, et al. Obesity and outcomes in premenopausal and postmenopausal breast cancer. Cancer Epidemiol Biomarkers Prev. 2005;14:1686–91.PubMed
63.
von Drygalski A, Tran TB, Messer K, et al. Obesity is an independent predictor of poor survival in metastatic breast cancer: retrospective analysis of a patient cohort whose treatment included high-dose chemotherapy and autologous stem cell support. Int J Breast Cancer. 2011;2011:523276.
64.
Zhao Y, Nichols JE, Valdez R, Mendelson CR, Simpson ER. Tumor necrosis factor-alpha stimulates aromatase gene expression in human adipose stromal cells through use of an activating protein-1 binding site upstream of promoter 1.4. Mol Endocrinol. 1996;10:1350–7.PubMed
65.
Chen D, Reierstad S, Lin Z, et al. Prostaglandin E(2) induces breast cancer related aromatase promoters via activation of p38 and c-Jun NH(2)-terminal kinase in adipose fibroblasts. Cancer Res. 2007;67:8914–22.PubMed
66.
O’Neill JS, Elton RA, Miller WR. Aromatase activity in adipose tissue from breast quadrants: a link with tumour site. Br Med J (Clin Res Ed). 1988;296:741–3.
67.
Bulun SE, Simpson ER. Regulation of aromatase expression in human tissues. Breast Cancer Res Treat. 1994;30:19–29.PubMed
68.
Sethi JK, Hotamisligil GS. The role of TNF alpha in adipocyte metabolism. Semin Cell Dev Biol. 1999;10:19–29.PubMed
69.
Prins JB, Niesler CU, Winterford CM, et al. Tumor necrosis factor-alpha induces apoptosis of human adipose cells. Diabetes. 1997;46:1939–44.PubMed
70.
Engelman JA, Berg AH, Lewis RY, Lisanti MP, Scherer PE. Tumor necrosis factor alpha-mediated insulin resistance, but not dedifferentiation, is abrogated by MEK1/2 inhibitors in 3T3-L1 adipocytes. Mol Endocrinol. 2000;14:1557–69.PubMed
71.
Nieman KM, Romero IL, Van Houten B, Lengyel E. Adipose tissue and adipocytes support tumorigenesis and metastasis. Biochim.Biophys Acta. 2013.
72.
Baglietto L, English DR, Hopper JL, et al. Circulating steroid hormone concentrations in postmenopausal women in relation to body size and composition. Breast Cancer Res Treat. 2009;115:171–9.PubMed
73.
Key T, Appleby P, Barnes I, Reeves G, Endogenous Hormones and Breast Cancer Collaborative Group. Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies. J Natl Cancer Inst. 2002;94:606–16.PubMed
74.
Zeleniuch-Jacquotte A, Shore RE, Koenig KL, et al. Postmenopausal levels of oestrogen, androgen, and SHBG and breast cancer: long-term results of a prospective study. Br J Cancer. 2004;90:153–9.PubMed
75.
Rinaldi S, Key TJ, Peeters PH, et al. Anthropometric measures, endogenous sex steroids and breast cancer risk in postmenopausal women: a study within the EPIC cohort. Int J Cancer. 2006;118:2832–9.PubMed
76.
Simpson ER, Davis SR. Minireview: aromatase and the regulation of estrogen biosynthesis–some new perspectives. Endocrinology. 2001;142:4589–94.PubMed
77.
Tekmal RR, Kirma N, Gill K, Fowler K. Aromatase overexpression and breast hyperplasia, an in vivo model–continued overexpression of aromatase is sufficient to maintain hyperplasia without circulating estrogens, and aromatase inhibitors abrogate these preneoplastic changes in mammary glands. Endocr Relat Cancer. 1999;6:307–14.PubMed
78.
Zeyda M, Stulnig TM. Obesity, inflammation, and insulin resistance—a mini-review. Gerontology. 2009;55:379–86.PubMed
79.
Fain JN, Madan AK, Hiler ML, Cheema P, Bahouth SW. Comparison of the release of adipokines by adipose tissue, adipose tissue matrix, and adipocytes from visceral and subcutaneous abdominal adipose tissues of obese humans. Endocrinology. 2004;145:2273–82.PubMed
80.
Fain JN. Release of inflammatory mediators by human adipose tissue is enhanced in obesity and primarily by the nonfat cells: a review. Mediat Inflamm. 2010;2010:513948.
81.
Iikuni N, Lam QL, Lu L, Matarese G, La Cava A. Leptin and Inflammation. Curr Immunol Rev. 2008;4:70–9.PubMed
82.
Ollberding NJ, Kim Y, Shvetsov YB, et al. Prediagnostic leptin, adiponectin, C-reactive protein, and the risk of postmenopausal breast cancer. Cancer Prev Res (Phila). 2013;6:188–95.
83.
Llanos AA, Dumitrescu RG, Marian C, et al. Adipokines in plasma and breast tissues: associations with breast cancer risk factors. Cancer Epidemiol Biomarkers Prev. 2012;21:1745–55.PubMed
84.
Villarreal-Molina MT, Antuna-Puente B. Adiponectin: anti-inflammatory and cardioprotective effects. Biochimie. 2012;94:2143–9.PubMed
85.
Grossmann ME, Ray A, Nkhata KJ, et al. Obesity and breast cancer: status of leptin and adiponectin in pathological processes. Cancer Metastasis Rev. 2010;29:641–53.PubMed
86.
Gross A, Newschaffer CJ, Hoffman Bolton JA, Rifai N, Visvanathan K. Adipocytokines, inflammation, and breast cancer risk in postmenopausal women: A prospective study. Cancer Epidemiol Biomarkers Prev. 2013.
87.
Wentworth JM, Naselli G, Brown WA, et al. Pro-inflammatory CD11c + CD206+ adipose tissue macrophages are associated with insulin resistance in human obesity. Diabetes. 2010;59:1648–56.PubMed
88.
Cancello R, Henegar C, Viguerie N, et al. Reduction of macrophage infiltration and chemoattractant gene expression changes in white adipose tissue of morbidly obese subjects after surgery-induced weight loss. Diabetes. 2005;54:2277–86.PubMed
89.
Nakanishi Y, Nakatsuji M, Seno H, et al. COX-2 inhibition alters the phenotype of tumor-associated macrophages from M2 to M1 in ApcMin/+ mouse polyps. Carcinogenesis. 2011;32:1333–9.PubMed
90.
Na YR, Yoon YN, Son DI, Seok SH. Cyclooxygenase-2 inhibition blocks M2 macrophage differentiation and suppresses metastasis in murine breast cancer model. PLoS One. 2013;8:e63451.PubMed
91.
Candido J, Hagemann T. Cancer-related inflammation. J Clin Immunol. 2013;33 Suppl 1:S79–84.PubMed
92.
Grivennikov SI, Karin M. Inflammatory cytokines in cancer: tumour necrosis factor and interleukin 6 take the stage. Ann Rheum Dis. 2011;70 Suppl 1:i104–8.PubMed
93.
Shah A, Mehta N, Reilly MP. Adipose inflammation, insulin resistance, and cardiovascular disease. JPEN J Parenter Enteral Nutr. 2008;32:638–44.PubMed
94.
Cinti S, Mitchell G, Barbatelli G, et al. Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res. 2005;46:2347–55.PubMed
95.
Stefan N, Kantartzis K, Machann J, et al. Identification and characterization of metabolically benign obesity in humans. Arch Intern Med. 2008;168:1609–16.PubMed
96.
Karelis AD, Faraj M, Bastard JP, et al. The metabolically healthy but obese individual presents a favorable inflammation profile. J Clin Endocrinol Metab. 2005;90:4145–50.PubMed
97.
Le KA, Mahurkar S, Alderete TL, et al. Subcutaneous adipose tissue macrophage infiltration is associated with hepatic and visceral fat deposition, hyperinsulinemia, and stimulation of NF-kappaB stress pathway. Diabetes. 2011;60:2802–9.PubMed
98.
Foroni C, Broggini M, Generali D, Damia G. Epithelial-mesenchymal transition and breast cancer: role, molecular mechanisms and clinical impact. Cancer Treat Rev. 2012;38:689–97.PubMed
99.
Karihtala P, Auvinen P, Kauppila S, Haapasaari KM, Jukkola-Vuorinen A, Soini Y. Vimentin, zeb1 and Sip1 are up-regulated in triple-negative and basal-like breast cancers: association with an aggressive tumour phenotype. Breast Cancer Res Treat. 2013;138:81–90.PubMed
100.
Kim S, Choi JH, Kim JB, et al. Berberine suppresses TNF-alpha-induced MMP-9 and cell invasion through inhibition of AP-1 activity in MDA-MB-231 human breast cancer cells. Molecules. 2008;13:2975–85.PubMed
101.
Wu Y, Deng J, Rychahou PG, Qiu S, Evers BM, Zhou BP. Stabilization of snail by NF-kappaB is required for inflammation-induced cell migration and invasion. Cancer Cell. 2009;15:416–28.PubMed
102.
Cho SG, Li D, Stafford LJ, et al. KiSS1 suppresses TNFalpha-induced breast cancer cell invasion via an inhibition of RhoA-mediated NF-kappaB activation. J Cell Biochem. 2009;107:1139–49.PubMed
103.
Hamaguchi T, Wakabayashi H, Matsumine A, Sudo A, Uchida A. TNF inhibitor suppresses bone metastasis in a breast cancer cell line. Biochem Biophys Res Commun. 2011;407:525–30.PubMed
104.
Dunlap SM, Chiao LJ, Nogueira L, et al. Dietary energy balance modulates epithelial-to-mesenchymal transition and tumor progression in murine claudin-low and basal-like mammary tumor models. Cancer Prev Res (Phila). 2012;5:930–42.
105.
Kushiro K, Chu RA, Verma A, Nunez NP. Adipocytes promote B16BL6 melanoma cell invasion and the epithelial-to-Mesenchymal Transition. Cancer Microenviron. 2012;5:73–82.PubMed
106.
Kushiro K, Nunez NP. Ob/ob serum promotes a mesenchymal cell phenotype in B16BL6 melanoma cells. Clin Exp Metastasis. 2011;28:877–86.PubMed
107.
Price RS, Cavazos DA, De Angel RE, Hursting SD, deGraffenried LA. Obesity-related systemic factors promote an invasive phenotype in prostate cancer cells. Prostate Cancer Prostatic Dis. 2012;15:135–43.PubMed
108.
Sehrawat A, Singh SV. Benzyl isothiocyanate inhibits epithelial-mesenchymal transition in cultured and xenografted human breast cancer cells. Cancer Prev Res (Phila). 2011;4:1107–17.
109.
Van Waes C. Nuclear factor-kappaB in development, prevention, and therapy of cancer. Clin Cancer Res. 2007;13:1076–82.PubMed
110.
Karin M. NF-kappaB as a critical link between inflammation and cancer. Cold Spring Harb Perspect Biol. 2009;1:a000141.PubMed
111.
Hagemann T, Wilson J, Kulbe H, et al. Macrophages induce invasiveness of epithelial cancer cells via NF-kappa B and JNK. J Immunol. 2005;175:1197–205.PubMed
112.
Hayden MS, Ghosh S. Shared principles in NF-kappaB signaling. Cell. 2008;132:344–62.PubMed
113.
Bonizzi G, Karin M. The two NF-kappaB activation pathways and their role in innate and adaptive immunity. Trends Immunol. 2004;25:280–8.PubMed
114.
Ahn KS, Aggarwal BB. Transcription factor NF-kappaB: a sensor for smoke and stress signals. Ann N Y Acad Sci. 2005;1056:218–33.PubMed
115.
Singh S, Shi Q, Bailey ST, et al. Nuclear factor-kappaB activation: a molecular therapeutic target for estrogen receptor-negative and epidermal growth factor receptor family receptor-positive human breast cancer. Mol Cancer Ther. 2007;6:1973–82.PubMed
116.
Ahmed A. Prognostic and therapeutic role of nuclear factor-kappa B (NF-kappaB) in breast cancer. J Ayub Med Coll Abbottabad. 2010;22:218–21.PubMed
117.
Yamaguchi N, Ito T, Azuma S, et al. Constitutive activation of nuclear factor-kappaB is preferentially involved in the proliferation of basal-like subtype breast cancer cell lines. Cancer Sci. 2009;100:1668–74.PubMed
118.
Sethi S, Sarkar FH, Ahmed Q, et al. Molecular markers of epithelial-to-mesenchymal transition are associated with tumor aggressiveness in breast carcinoma. Transl Oncol. 2011;4:222–6.PubMed
119.
Newton R, Kuitert LM, Slater DM, Adcock IM, Barnes PJ. Cytokine induction of cytosolic phospholipase A2 and cyclooxygenase-2 mRNA is suppressed by glucocorticoids in human epithelial cells. Life Sci. 1997;60:67–78.PubMed
120.
Hobbs SS, Goettel JA, Liang D, et al. TNF transactivation of EGFR stimulates cytoprotective COX-2 expression in gastrointestinal epithelial cells. Am J Physiol Gastrointest Liver Physiol. 2011;301:G220–9.PubMed
121.
Gonzalez-Periz A, Claria J. Resolution of adipose tissue inflammation. Sci World J. 2010;10:832–56.
122.
Long EK, Hellberg K, Foncea R, Hertzel AV, Suttles J, Bernlohr DA. Fatty acids induce leukotriene C4 synthesis in macrophages in a fatty acid binding protein-dependent manner. Biochim Biophys Acta. 1831;2013:1199–207.
123.
Funk CD. Prostaglandins and leukotrienes: advances in eicosanoid biology. Science. 2001;294:1871–5.PubMed
124.
Ristimaki A, Sivula A, Lundin J, et al. Prognostic significance of elevated cyclooxygenase-2 expression in breast cancer. Cancer Res. 2002;62:632–5.PubMed
125.
Denkert C, Winzer KJ, Muller BM, et al. Elevated expression of cyclooxygenase-2 is a negative prognostic factor for disease free survival and overall survival in patients with breast carcinoma. Cancer. 2003;97:2978–87.PubMed
126.
Denkert C, Winzer KJ, Hauptmann S. Prognostic impact of cyclooxygenase-2 in breast cancer. Clin Breast Cancer. 2004;4:428–33.PubMed
127.
Kim HS, Moon HG, Han W, et al. COX2 overexpression is a prognostic marker for Stage III breast cancer. Breast Cancer Res Treat. 2012;132:51–9.PubMed
128.
Mohammad AM, Abdel HA, Abdel W, Ahmed AM, Wael T, Eiman G. Expression of cyclooxygenase-2 and 12-lipoxygenase in human breast cancer and their relationship with HER-2/neu and hormonal receptors: impact on prognosis and therapy. Indian J Cancer. 2006;43:163–8.PubMed
129.
Dhakal HP, Naume B, Synnestvedt M, et al. Expression of cyclooxygenase-2 in invasive breast carcinomas and its prognostic impact. Histol Histopathol. 2012;27:1315–25.PubMed
130.
Baumgarten SC, Frasor J. Minireview: Inflammation: an instigator of more aggressive estrogen receptor (ER) positive breast cancers. Mol Endocrinol. 2012;26:360–71.PubMed
131.
Lykkesfeldt AE, Henriksen KL, Rasmussen BB, et al. In situ aromatase expression in primary tumor is associated with estrogen receptor expression but is not predictive of response to endocrine therapy in advanced breast cancer. BMC Cancer. 2009;9:185.PubMed
132.
Kang JH, Song KH, Jeong KC, et al. Involvement of Cox-2 in the metastatic potential of chemotherapy-resistant breast cancer cells. BMC Cancer. 2011;11:334.PubMed
133.
Martinez-Orozco R, Navarro-Tito N, Soto-Guzman A, Castro-Sanchez L, Perez SE. Arachidonic acid promotes epithelial-to-mesenchymal-like transition in mammary epithelial cells MCF10A. Eur J Cell Biol. 2010;89:476–88.PubMed
134.
Hughes R, Timmermans P, Schrey MP. Regulation of arachidonic acid metabolism, aromatase activity and growth in human breast cancer cells by interleukin-1beta and phorbol ester: dissociation of a mediatory role for prostaglandin E2 in the autocrine control of cell function. Int J Cancer. 1996;67:684–9.PubMed
135.
Rose DP, Connolly JM. Effects of fatty acids and inhibitors of eicosanoid synthesis on the growth of a human breast cancer cell line in culture. Cancer Res. 1990;50:7139–44.PubMed
136.
Liu XH, Connolly JM, Rose DP. The 12-lipoxygenase gene-transfected MCF-7 human breast cancer cell line exhibits estrogen-independent, but estrogen and omega-6 fatty acid-stimulated proliferation in vitro, and enhanced growth in athymic nude mice. Cancer Lett. 1996;109:223–30.PubMed
137.
Connolly JM, Rose DP. Enhanced angiogenesis and growth of 12-lipoxygenase gene-transfected MCF-7 human breast cancer cells in athymic nude mice. Cancer Lett. 1998;132:107–12.PubMed
138.
Avis I, Hong SH, Martinez A, et al. Five-lipoxygenase inhibitors can mediate apoptosis in human breast cancer cell lines through complex eicosanoid interactions. FASEB J. 2001;15:2007–9.PubMed
139.
Tong WG, Ding XZ, Adrian TE. The mechanisms of lipoxygenase inhibitor-induced apoptosis in human breast cancer cells. Biochem Biophys Res Commun. 2002;296:942–8.PubMed
140.
Natarajan R, Esworthy R, Bai W, Gu JL, Wilczynski S, Nadler J. Increased 12-lipoxygenase expression in breast cancer tissues and cells. Regulation by epidermal growth factor. J Clin Endocrinol Metab. 1997;82:1790–8.PubMed
141.
Jiang WG, Douglas-Jones A, Mansel RE. Levels of expression of lipoxygenases and cyclooxygenase-2 in human breast cancer. Prostaglandins Leukot Essent Fat Acids. 2003;69:275–81.
142.
Fulton AM, Ma X, Kundu N. Targeting prostaglandin E EP receptors to inhibit metastasis. Cancer Res. 2006;66:9794–7.PubMed
143.
Guo Y, Zhang W, Giroux C, et al. Identification of the orphan G protein-coupled receptor GPR31 as a receptor for 12-(S)-hydroxyeicosatetraenoic acid. J Biol Chem. 2011;286:33832–40.PubMed
144.
Liu XH, Connolly JM, Rose DP. Eicosanoids as mediators of linoleic acid-stimulated invasion and type IV collagenase production by a metastatic human breast cancer cell line. Clin Exp Metastasis. 1996;14:145–52.PubMed
145.
Timoshenko AV, Xu G, Chakrabarti S, Lala PK, Chakraborty C. Role of prostaglandin E2 receptors in migration of murine and human breast cancer cells. Exp Cell Res. 2003;289:265–74.PubMed
146.
Larkins TL, Nowell M, Singh S, Sanford GL. Inhibition of cyclooxygenase-2 decreases breast cancer cell motility, invasion and matrix metalloproteinase expression. BMC Cancer. 2006;6:181.PubMed
147.
Serna-Marquez N, Villegas-Comonfort S, Galindo-Hernandez O, Navarro-Tito N, Millan A, Salazar EP. Role of LOXs and COX-2 on FAK activation and cell migration induced by linoleic acid in MDA-MB-231 breast cancer cells. Cell Oncol (Dordr). 2013;36:65–77.
148.
Singh B, Berry JA, Shoher A, Ramakrishnan V, Lucci A. COX-2 overexpression increases motility and invasion of breast cancer cells. Int J Oncol. 2005;26:1393–9.PubMed
149.
Morris PG, Zhou XK, Milne GL, et al. Increased levels of urinary PGE-M, a biomarker of inflammation, occur in association with obesity, aging, and lung metastases in patients with breast cancer. Cancer Prev Res (Phila). 2013;6:428–36.
150.
Kim S, Taylor JA, Milne GL, Sandler DP. Association between urinary prostaglandin E2 metabolite and breast cancer risk: a prospective, Case-Cohort Study of Postmenopausal Women. Cancer Prev Res (Phila). 2013;6:511–8.
151.
Uzzan B, Nicolas P, Cucherat M, Perret GY. Microvessel density as a prognostic factor in women with breast cancer: a systematic review of the literature and meta-analysis. Cancer Res. 2004;64:2941–55.PubMed
152.
Pang C, Gao Z, Yin J, Zhang J, Jia W, Ye J. Macrophage infiltration into adipose tissue may promote angiogenesis for adipose tissue remodeling in obesity. Am J Physiol Endocrinol Metab. 2008;295:E313–22.PubMed
153.
Christiaens V, Lijnen HR. Angiogenesis and development of adipose tissue. Mol Cell Endocrinol. 2010;318:2–9.PubMed
154.
Wada H, Ura S, Kitaoka S, et al. Distinct characteristics of circulating vascular endothelial growth factor-a and C levels in human subjects. PLoS One. 2011;6:e29351.PubMed
155.
Vona-Davis L, Rose DP. Angiogenesis, adipokines and breast cancer. Cytokine Growth Factor Rev. 2009;20:193–201.PubMed
156.
Rose DP, Connolly JM. Regulation of tumor angiogenesis by dietary fatty acids and eicosanoids. Nutr Cancer. 2000;37:119–27.PubMed
157.
Ye J. Adipose tissue vascularization: its role in chronic inflammation. Curr Diab Rep. 2011;11:203–10.PubMed
158.
Ono M. Molecular links between tumor angiogenesis and inflammation: inflammatory stimuli of macrophages and cancer cells as targets for therapeutic strategy. Cancer Sci. 2008;99:1501–6.PubMed
159.
Zhang Y, Daaka Y. PGE2 promotes angiogenesis through EP4 and PKA Cgamma pathway. Blood. 2011;118:5355–64.PubMed
160.
Ninomiya I, Nagai N, Oyama K, et al. Antitumor and anti-metastatic effects of cyclooxygenase-2 inhibition by celecoxib on human colorectal carcinoma xenografts in nude mouse rectum. Oncol Rep. 2012;28:777–84.PubMed
161.
Prosperi JR, Mallery SR, Kigerl KA, Erfurt AA, Robertson FM. Invasive and angiogenic phenotype of MCF-7 human breast tumor cells expressing human cyclooxygenase-2. Prostaglandins Other Lipid Mediat. 2004;73:249–64.PubMed
162.
Nie D, Tang K, Szekeres K, Li L, Honn KV. Eicosanoid regulation of angiogenesis in human prostate carcinoma and its therapeutic implications. Ann N Y Acad Sci. 2000;905:165–76.PubMed
163.
Nie D, Krishnamoorthy S, Jin R, et al. Mechanisms regulating tumor angiogenesis by 12-lipoxygenase in prostate cancer cells. J Biol Chem. 2006;281:18601–9.PubMed
164.
Chatterjee M, Das S, Roy K, Chatterjee M. Overexpression of 5-lipoxygenase and its relation with cell proliferation and angiogenesis in 7,12-dimethylbenz(alpha)anthracene-induced rat mammary carcinogenesis. Mol Carcinog. 2013;52:359–69.PubMed
165.
Sexton KR, Franzini L, Day RS, Brewster A, Vernon SW, Bondy ML. A review of body size and breast cancer risk in Hispanic and African American women. Cancer. 2011;117:5271–81.PubMed
166.
Hyatt TC, Phadke RP, Hunter GR, Bush NC, Munoz AJ, Gower BA. Insulin sensitivity in African-American and white women: association with inflammation. Obesity (Silver Spring). 2009;17:276–82.
167.
Colditz GA, Willett WC, Stampfer MJ, et al. Weight as a risk factor for clinical diabetes in women. Am J Epidemiol. 1990;132:501–13.PubMed
168.
Autier P, Koechlin A, Boniol M, et al. Serum insulin and C-peptide concentration and breast cancer: a meta-analysis. Cancer Causes Control. 2013;24:873–83.PubMed
169.
Rose DP, Vona-Davis L. The cellular and molecular mechanisms by which insulin influences breast cancer risk and progression. Endocr Relat Cancer. 2012;19:R225–41.PubMed
170.
Blackburn GL, Wang KA. Dietary fat reduction and breast cancer outcome: results from the Women’s Intervention Nutrition Study (WINS). Am J Clin Nutr. 2007;86:s878–81.PubMed
Metadata
Title
The Obesity-Inflammation-Eicosanoid Axis in Breast Cancer
Authors
Linda Vona-Davis
David P. Rose
Publication date
01-12-2013
Publisher
Springer US
Published in
Journal of Mammary Gland Biology and Neoplasia / Issue 3-4/2013
Print ISSN: 1083-3021
Electronic ISSN: 1573-7039
DOI
https://doi.org/10.1007/s10911-013-9299-z

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