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Adipose Tissue, Obesity and Adiponectin: Role in Endocrine Cancer Risk.

ABSTRACT: Adipose tissue has been recognized as a complex organ with endocrine and metabolic roles. The excess of fat mass, as occurs during overweight and obesity states, alters the regulation of adipose tissue, contributing to the development of obesity-related disorders. In this regard, many epidemiological studies shown an association between obesity and numerous types of malignancies, comprising those linked to the endocrine system (e.g., breast, endometrial, ovarian, thyroid and prostate cancers). Multiple factors may contribute to this phenomenon, such as hyperinsulinemia, dyslipidemia, oxidative stress, inflammation, abnormal adipokines secretion and metabolism. Among adipokines, growing interest has been placed in recent years on adiponectin (APN) and on its role in carcinogenesis. APN is secreted by adipose tissue and exerts both anti-inflammatory and anti-proliferative actions. It has been demonstrated that APN is drastically decreased in obese individuals and that it can play a crucial role in tumor growth. Although literature data on the impact of APN on carcinogenesis are sometimes conflicting, the most accredited hypothesis is that it has a protective action, preventing cancer development and progression. The aim of the present review is to summarize the currently available evidence on the involvement of APN and its signaling in the etiology of cancer, focusing on endocrine malignancies.

SUBMITTER: Tumminia A

PROVIDER: S-EPMC6628240 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Adipose Tissue, Obesity and Adiponectin: Role in Endocrine Cancer Risk.

Tumminia Andrea A Vinciguerra Federica F Parisi Miriam M Graziano Marco M Sciacca Laura L Baratta Roberto R Frittitta Lucia L

International journal of molecular sciences 20190612 12

Adipose tissue has been recognized as a complex organ with endocrine and metabolic roles. The excess of fat mass, as occurs during overweight and obesity states, alters the regulation of adipose tissue, contributing to the development of obesity-related disorders. In this regard, many epidemiological studies shown an association between obesity and numerous types of malignancies, comprising those linked to the endocrine system (e.g., breast, endometrial, ovarian, thyroid and prostate cancers). M ...[more]

PMID: 31212761

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Project description:BackgroundInflammatory breast cancer (IBC) represents a deadly aggressive phenotype of breast cancer (BC) with a unique clinicopathological presentation and low survival rate. In fact, obesity represents an important risk factor for BC. Although several studies have identified different cellular-derived and molecular factors involved in IBC progression, the role of adipocytes remains unclear. Cancer-associated adipose tissue (CAAT) expresses a variety of adipokines, which contribute to tumorigenesis and the regulation of cancer stem cell (CSC). This research investigated the potential effect of the secretome of CAAT explants from patients with BC on the progression and metastasis of the disease.MethodsThis study established an ex-vivo culture of CAAT excised from IBC (n = 13) vs. non-IBC (n = 31) patients with obesity and profiled their secretome using a cytokine antibody array. Furthermore, the quantitative PCR (qPCR) methodology was used to validate the levels of predominant cytokines at the transcript level after culture in a medium conditioned by CAAT. Moreover, the impact of the CAAT secretome on the expression of epithelial-mesenchymal transition (EMT) and cells with stem cell (CSC) markers was studied in the non-IBC MDA-MB-231 and the IBC SUM-149 cell lines. The statistical differences between variables were evaluated using the chi-squared test and unpaired a Student's t-test.ResultsThe results of cytokine array profiling revealed an overall significantly higher level of a panel of 28 cytokines secreted by the CAAT ex-vivo culture from IBC patients with obesity compared to those with non-IBC. Of note, interleukin-6 (IL-6), interleukin-8 (IL-8), and monocyte chemo-attractant protein 1 (MCP-1) were the major adipokines secreted by the CAAT IBC patients with obesity. Moreover, the qPCR results indicated a significant upregulation of the IL-6, IL-8, and MCP-1 mRNAs in CAAT ex-vivo culture of patients with IBC vs. those with non-IBC. Intriguingly, a qPCR data analysis showed that the CAAT secretome secretions from patients with non-IBC downregulated the mRNA levels of the CD24 CSC marker and of the epithelial marker E-cadherin in the non-IBC cell line. By contrast, E-cadherin was upregulated in the SUM-149 cell.ConclusionsThis study identified the overexpression of IL-6, IL-8, and MCP-1 as prognostic markers of CAAT from patients with IBC but not from those with non-IBC ; moreover, their upregulation might be associated with IBC aggressiveness via the regulation of CSC and EMT markers. This study proposed that targeting IL-6, IL-8, and MCP-1 may represent a therapeutic option that should be considered in the treatment of patients with IBC.

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Dataset Information

Adipose Tissue, Obesity and Adiponectin: Role in Endocrine Cancer Risk.

Publications

Adipose Tissue, Obesity and Adiponectin: Role in Endocrine Cancer Risk.

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