Total and High-Molecular-Weight Adiponectin in Breast Cancer: In Vitro and in Vivo Studies

University of Leipzig, Leipzig, Saxony, Germany
Journal of Clinical Endocrinology &amp Metabolism (Impact Factor: 6.21). 04/2007; 92(3):1041-8. DOI: 10.1210/jc.2006-1858
Source: PubMed

ABSTRACT Obesity is a major risk factor for breast cancer. We hypothesized that obesity-induced decreases in total and/or high-molecular-weight (HMW) adiponectin levels may underlie this association.
We measured serum total and HMW adiponectin in a hospital-based case-control study of 74 female breast cancer patients and 76 controls. In parallel, expression of adiponectin and its receptors AdipoR1/R2 were measured in tissue samples using RT-PCR, and protein expression of AdipoR1/R2 was localized and quantified using immunohistochemistry. Finally, we documented AdipoR1/R2 expression in several breast cancer cell lines and studied adiponectin signaling and the effect of adiponectin on proliferation in the T47D breast cancer cell line in vitro.
Women with the highest adiponectin levels had a 65% reduced risk of breast cancer (P = 0.04). This association became stronger after adjustment for age, body mass index, and hormonal and reproductive factors (P = 0.02). Modeling HMW instead of total adiponectin produced similar results and did not offer any additional predictive value. Breast cancer cells expressed AdipoR1/R2 but not adiponectin. Expression of AdipoR1, but not AdipoR2, was higher in tumor tissue than both adjacent and control tissues. Exposure of T47D cells to adiponectin significantly inhibited the percentage of viable cells to 86% and proliferation to 66% but had no effect on apoptosis. These effects were associated with activation of ERK1/2 but not AMP-activated protein kinase or p38MAPK.
These studies suggest that adiponectin may act as a biomarker of carcinogenesis and may constitute a molecular link between obesity and breast cancer.

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Available from: Theodoros Kelesidis, Sep 28, 2015
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    • "The findings showed that adiponectin decreased cell proliferation in human endometrial cancerous tissue via adiponectin receptors and the level of Adipo R1 expression was higher than that of Adipo R2 but the level of expression of receptors in cancerous tissue did not indicate significant difference compared to normal non-cancerous tissue (30). The recent research has indicated that expression of Adipo R1 in breast cancer cells (32) and human endometrial cancerous tissue (23) is higher than th at of Adipo R2. "
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    ABSTRACT: Adiponectin is one of the most important adipokines secreted from fatty tissue that has a direct inhibitory effect on the development of cancer cells. Adiponectin plays an important role in human reproduction system and fertility of women. Adiponectin concentration decreases in women with endometriosis and endometrial cancer. The aim of the present study was to investigate the effect of adiponectin on human endometrial stromal cell (HESC) viability as well as mRNA expression of Adipo R1 and Adipo R2 receptors. In this experimental study, eight endometrial biopsies were taken and stromal cells were separated by enzymatic digestion and cell filtrations. Stromal cells of each biopsy were divided into four groups: control, 10, 100, and 200 ng/ml adiponectin concentrations. The effect of adiponectin on viability of the normal HESCs was studied by trypan blue staining and the relative expression levels of Adipo R1 and R2 were analyzed by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). Data were analyzed by one way ANOVA and unpaired student's t test and p<0.05 was considered significant. Adiponectin decreased viability of normal human endometrial stromal cells in a dose and time dependent manner. Expression of Adipo R1 and Adipo R2 receptors did not change in the presence of adiponectin. Adiponectin can directly influence the viability of HESCs and decrease their viability, but it didn't change expression of adiponectin receptors.
    International journal of fertility & sterility 04/2013; 7(1):43-8. · 0.47 Impact Factor
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    • "These conditions are associated with changes in several hormonal systems, including insulin, estrogen, cytokines and growth factors [3]. Recent studies have linked breast cancer with insulin resistance [9-11]; metabolic syndrome (MetS) [12,13], and altered adipokine levels [14]. "
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    ABSTRACT: Background Obesity has been linked to many adverse health consequences, including breast cancer. This study aims to determine adipocytokine and other biological changes in recently diagnosed breast cancer patients before therapy is started. Methods A total of 109 female Saudi subjects [56 newly diagnosed, treatment-naïve, histologically-confirmed breast cancer cases and 53 age- and BMI-matched controls] were enrolled in this study. Anthropometric data were collected. Serum insulin, adipocytokines and plasminogen activator inhibitor-1 (PAI-1) concentrations were measured using a customized multiplex Luminex assay. Hypersensitive C-Reactive Protein (CRP), tumor necrosis factor-alpha (TNF-α), and angiotensin II (ANG II) were measured using ELISA. Results A few days in the diagnosis, breast cancer subjects had significantly higher systolic blood pressure (p = 0.03), glucose (p = 0.01), triglycerides (p = 0.001), leptin (p = 0.044), resistin (p = 0.04), ANG II (p = 0.02), TNF-α (p = 0.045), and CRP (p = 0.04) than the controls. On the other hand, HDL (p = 0.01) and adiponectin (p = 0.02) were significantly lower in cancer subjects than controls. A significant association was found between elevated triglycerides (TG) and breast cancer [OR (95% CI), 6.1(1.8, 15.6), p = 0.004], as well as elevated ANG II [OR (95% CI), 5.2(1.2, 14.3), p = 0.03]. On the other hand, aPAI and HDL correlated negatively with breast cancer [OR (95% CI), 0.076(0.01, 0.34), p = 0.001; 0.30(0.09, 0.95), p 0.04, respectively]. Conclusion Circulating ANGII and triglycerides were positively associated with early breast cancer. In contrast, HDL-cholesterol correlated negatively with ANG II and aPAI in these patients. This suggests that patients with recently diagnosed breast cancer have biochemical changes consistent with an activated stress response and/or that patients with metabolic syndrome manifestations have a higher risk of developing this disease.
    BMC Cancer 02/2013; 13(1):54. DOI:10.1186/1471-2407-13-54 · 3.36 Impact Factor
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    • "Studies have shown that APN levels affect the phenotypic characterization of tumors in breast cancer. Decreased serum APN concentrations have been associated with a higher risk of breast cancer[55,56] and aggressive tumors characterized by increased size, histological score, and estrogen receptor negativity[57]. These attributes are seen in estrogen/progesterone receptor negative breast cancers and suggest that decreased APN may be caused by the deregulation of sex steroid homeostasis[58]. The role of APN in preventing breast tumorigenesis is intertwined with endocrine and paracrine factors. "
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    ABSTRACT: Adiponectin (APN), a novel hormone/cytokine derived from adipocyte tissue, is involved in various physiological functions. Genetics, nutrition, and adiposity are factors contributing to circulating plasma concentrations of APN. Clinical correlation studies have shown that lower levels of serum APN are associated with increased malignancy of various cancers, such as breast and colon cancers, suggesting that APN has a role in tumorigenesis. APN affects insulin resistance, thus further influencing cancer development. Tumor cells may express receptors for APN. Cellular signaling is the mechanism by which APN exerts its host-protective responses. These factors suggest that serum APN levels and downstream signaling targets of APN may serve as potential diagnostic markers for malignancies. Further research is necessary to clarify the exact role of APN in cancer diagnosis and therapy.
    Cancer Biology and Medicine 12/2012; 9(4):213-220. DOI:10.7497/j.issn.2095-3941.2012.04.001
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