Role of adipokines and cytokines in obesity-associated breast cancer: Therapeutic targets

Khan, Sajid; Shukla, Samriddhi; Sinha, Sonam; Meeran, Syed Musthapa

doi:10.1016/j.cytogfr.2013.10.001

Cited by 140 publications

(129 citation statements)

References 129 publications

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“…50 The effect of leptin on oestrogenindependent breast cancers, however, has remained controversial. A study by Colbert et al in 67 Chinese patients with breast cancer demonstrated that more than 61% of breast cancer tissues, which included oestrogen receptor positive, oestrogen receptor negative and triple (oestrogen, progesterone and HER2 receptors) negative tumours, were stained positive for leptin and its receptor. Furthermore, leptin and its receptor were positively associated with proangiogenic factors such as Notch and vascular endothelial growth factor (VEGF) and hence implicated in tumour aggressiveness and poorer prognosis.…”

Section: Leptin and Breast Cancermentioning

confidence: 99%

“…30 Pegylated leptin-receptor antagonist 2 (PEG-LPrA2) are also being tested in preclinical studies to reduce the proliferation and angiogenesis of breast cancer cells. 67 Preclinical studies have shown that monoclonal antibodies against IL-6 and its receptors can significantly inhibit tumour growth either alone or in combination with conventional chemotherapy. Among them, siltuximab, a monoclonal antibody against IL-6, is being evaluated in phase 2 clinical trials against transplant-refractory multiple myeloma, hormone-refractory prostate cancer and metastatic renal cell carcinoma.…”

Section: Clinical and Therapeutic Implicationsmentioning

confidence: 99%

“…As adiponectin itself is difficult to synthesize, synthetic small peptides like ADP-355, which can mimic the action of adiponectin, are being tested in preclinical studies to restrict proliferation of several adiponectin receptor-positive cancer cell lines. 67 Furthermore, as HMW adiponectin constitutes the most active oligomeric form of adiponectin, a novel class of nonthiazolidinedione peroxisome proliferator-activated receptor (PPAR) ligand, AMG131, has been developed to increase the ratio of high molecular weight to total adiponectin concentrations in the circulation. 30 Pegylated leptin-receptor antagonist 2 (PEG-LPrA2) are also being tested in preclinical studies to reduce the proliferation and angiogenesis of breast cancer cells.…”

Section: Clinical and Therapeutic Implicationsmentioning

confidence: 99%

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Obesity, adipokines and cancer: an update

Lee

Woo

Wang

et al. 2014

Clinical Endocrinology

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SummaryObesity causes dysfunction of adipose tissue, with resultant chronic inflammation and adverse interplay of various adipokines, sex steroids and endocrine hormones. All these drive tumourigenesis and explain the epidemiological link between obesity and cancer. Over the past decade, the associations among obesity, adipokines and cancer have been increasingly recognized. Adipokines and their respective signalling pathways have drawn much research attention in the field of oncology and cancer therapeutics. This review will discuss the recent advances in the understanding of the association of several adipokines with common obesity-related cancers and the clinical therapeutic implications.

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Section: Leptin and Breast Cancermentioning

confidence: 99%

Section: Clinical and Therapeutic Implicationsmentioning

confidence: 99%

Section: Clinical and Therapeutic Implicationsmentioning

confidence: 99%

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Obesity, adipokines and cancer: an update

Lee

Woo

Wang

et al. 2014

Clinical Endocrinology

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“…Several possible mechanisms have been suggested: i) Obese people often have increased levels of insulin and insulin-like growth factor-1 in their blood, which may promote the development of tumors (Belardi et al, 2013), ii) Adipose tissue produces hormones, called adipokines such as leptine and adiponectine, that may stimulate angiogenesis, growth of malignant cells (Grossmann et al, 2010;Khan et al, 2013) and that may modulate anti-tumor immune response (Catalan et al, 2013) iii) Finally, obesity is associated with elevated levels of pro-inflammatory cytokines (Harvey et al, 2011) which generate a low grade chronic inflammatory state that may be involved on cancer development (Hanahan and Weinberg, 2011;Ferguson et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Breast Cancer in Tunisia: Association of Body Mass Index with Histopathological Aspects of Tumors

Bouguerra

Guissouma²,

Labidi³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Background: Previous studies have suggested a link between obesity and breast cancer (BC). However, there is no universal consensus, especially in population based studies. Because only few studies have been conducted on African women, we aimed here to assess the relationship between BMI at time of diagnosis and the BC histopathological features among Tunisian patients according to menopausal status using a hospital-based prospective cohort study. Materials and Methods: Clinical and pathological data were collected from 262 patients stratified on four groups according to their BMI. The relationship between BMI and histopathological features at diagnosis was analysed using univariate and multivariate analysis. Receiver-operating characteristic (ROC) curves were used to evaluate the performance of BMI in predicting of high tumor grade, in comparison to ki-67 index of proliferation. Results: Obesity was correlated with larger tumors, advanced grade and with ER-PRHer2+ BC subtype. An association of BMI with tumor size and tumor grade was observed in both premenopausal and postmenopausal women. Additionally, a significant association between BMI and ER+, ER+PR+Her2+ and ER-PR-Her2+ status was revealed for premenopausal patients, while only ER+PR+Her2+ was associated with BMI for postmenopausal women. Finally, our results showed that compared to Ki67 proliferation index, BMI is a useful prognostic marker of high grade BC tumors. Conclusions: These data are the first to show that in Tunisia obese women suffering from BC have significantly larger tumors and advanced tumor grade and that higher BMI might influence tumor characteristics and behavior.

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“…Obesity leads to altered expression of adipokines and cytokines, including TNF-α, IL-6, IL1β. 26 Cancer-associated inflammation also occurs in conjunction with specific cell types, including pro-inflammatory cytokines. 13 As part of this low-grade inflammatory state associated with obesity, overproduction of cytokines may influence the risk of initial BC cancer development as well as its progression.…”

Section: Insulin Resistance and Inflammation In Breast Cancer -Griffimentioning

confidence: 99%

Insulin Resistance and Inflammation in Black Women with and without Breast Cancer: Cause for Concern

et al. 2016

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Objective: After chemotherapy for breast cancer, Black women gain more weight and have an increased mortality rate compared with White women. Our study objective was to compare biomarkers associated with obesity in Black women with and without a history of breast cancer.Design: Case-controlSetting: Academic/federal institutionParticipants: Black women with a history of breast cancer (cases) and age-matched controls.Methods: We compared insulin resistance, inflammation, and lipids in overweight and obese Black women with a history of breast cancer (n=19), age similar controls (n=25), and older controls (n=32). Groups did not differ on mean body mass index (BMI), which was 35.4 kg/m2, 36.0 kg/m2, and 33.0 kg/m2, respectively.Main Outcome Measures: Insulin resistance (HOMA-IR); inflammation (TNF-α, IL-1b, IL-6, IL-8, CRP); lipids (cholesterol, triglycerides).Results: Cases had 1.6 and 1.38 times higher HOMA-IR values compared with age similar and older controls, respectively (P≤.001 for both). TNF-α and IL-1b were significantly higher in cases compared with both control groups (P<.001 for both). IL-6 was also higher in cases compared with age-similar controls (P=.007), and IL-8 was lower in cases compared with older controls (P<.05). Lipids did not differ between cases and either control group.Conclusions: Black women with breast cancer were significantly more insulin resistant with increased inflammation compared not only with age similar controls but with women who were, on average, a decade older. These biomarkers of insulin resistance and inflammation may be associated with increased risk of breast cancer recurrence and require ongoing evaluation, especially given the relatively abnormal findings compared with the controls in this underserved group. Ethn Dis. 2016;26(4):513-520; doi:10.18865/ed.26.4.513

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Role of adipokines and cytokines in obesity-associated breast cancer: Therapeutic targets

Cited by 140 publications

References 129 publications

Obesity, adipokines and cancer: an update

Obesity, adipokines and cancer: an update

Breast Cancer in Tunisia: Association of Body Mass Index with Histopathological Aspects of Tumors

Insulin Resistance and Inflammation in Black Women with and without Breast Cancer: Cause for Concern

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