Cellular and Molecular Players in the Interplay between Adipose Tissue and Breast Cancer (original) (raw)
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Molecular Links between Central Obesity and Breast Cancer
International Journal of Molecular Sciences, 2019
Worldwide, breast cancer (BC) is the most common malignancy in women, in regard to incidence and mortality. In recent years, the negative role of obesity during BC development and progression has been made abundantly clear in several studies. However, the distribution of body fat may be more important to analyze than the overall body weight. In our review of literature, we reported some key findings regarding the role of obesity in BC development, but focused more on central adiposity. Firstly, the adipose microenvironment in obese people bears many similarities with the tumor microenvironment, in respect to associated cellular composition, chronic low-grade inflammation, and high ratio of reactive oxygen species to antioxidants. Secondly, the adipose tissue functions as an endocrine organ, which in obese people produces a high level of tumor-promoting hormones, such as leptin and estrogen, and a low level of the tumor suppressor hormone, adiponectin. As follows, in BC this leads to the activation of oncogenic signaling pathways: NFκB, JAK, STAT3, AKT. Moreover, overall obesity, but especially central obesity, promotes a systemic and local low grade chronic inflammation that further stimulates the increase of tumor-promoting oxidative stress. Lastly, there is a constant exchange of information between BC cells and adipocytes, mediated especially by extracellular vesicles, and which changes the transcription profile of both cell types to an oncogenic one with the help of regulatory non-coding RNAs.
The Importance of Breast Adipose Tissue in Breast Cancer
International Journal of Molecular Sciences
Adipose tissue is a complex endocrine organ, with a role in obesity and cancer. Adipose tissue is generally linked to excessive body fat, and it is well known that the female breast is rich in adipose tissue. Hence, one can wonder: what is the role of adipose tissue in the breast and why is it required? Adipose tissue as an organ consists of adipocytes, an extracellular matrix (ECM) and immune cells, with a significant role in the dynamics of breast changes throughout the life span of a female breast from puberty, pregnancy, lactation and involution. In this review, we will discuss the importance of breast adipose tissue in breast development and its involvement in breast changes happening during pregnancy, lactation and involution. We will focus on understanding the biology of breast adipose tissue, with an overview on its involvement in the various steps of breast cancer development and progression. The interaction between the breast adipose tissue surrounding cancer cells and vic...
Molecular links between obesity and breast cancer
Endocrine Related Cancer, 2006
Breast cancer continues to be a major health problem for women in the USA and worldwide. There is a need to identify and take steps to alter modifiable breast cancer risks. Conditions of obesity and overweight are risk factors that have reached epidemic proportions. This article reviews the evidence in the literature that test mechanism-based hypotheses which attempt to provide a molecular basis for a causal link between obesity and breast cancer risk, particularly the effects of metabolic syndrome and insulin resistance, peripheral estrogen aromatization in adipose tissue, and direct effect of adipokines. Future areas for study and implications for therapy are discussed.
Cells, 2019
Obesity is a global pandemic and it is well evident that obesity is associated with the development of many disorders including many cancer types. Breast cancer is one of that associated with a high mortality rate. Adipocytes, a major cellular component in adipose tissue, are dysfunctional during obesity and also known to promote breast cancer development both in vitro and in vivo. Dysfunctional adipocytes can release metabolic substrates, adipokines, and cytokines, which promote proliferation, progression, invasion, and migration of breast cancer cells. The secretion of adipocytes can alter gene expression profile, induce inflammation and hypoxia, as well as inhibit apoptosis. It is known that excessive free fatty acids, cholesterol, triglycerides, hormones, leptin, interleukins, and chemokines upregulate breast cancer development. Interestingly, adiponectin is the only adipokine that has anti-tumor properties. Moreover, adipocytes are also related to chemotherapeutic resistance, resulting in the poorer outcome of treatment and advanced stages in breast cancer. Evaluation of the adipocyte secretion levels in the circulation can be useful for prognosis and evaluation of the effectiveness of cancer therapy in the patients. Therefore, understanding about functions of adipocytes as well as obesity in breast cancer may reveal novel targets that support the development of new anti-tumor therapy. In this systemic review, we summarize and update the effects of secreted factors by adipocytes on the regulation of breast cancer in the tumor microenvironment.
Diabetes, 2014
Obesity is often regarded as the primary cause of metabolic syndrome. However, many lines of evidence suggest that obesity may develop as a protective mechanism against tissue damage during caloric surplus and that it is only when the maximum fat accumulation capacity is reached and fatty acid spillover occurs into to peripheral tissues that metabolic diseases develop. In this regard, identifying the molecular mechanisms that modulate adipocyte fat accumulation and fatty acid spillover is imperative. Here we identify the deleted in breast cancer 1 (DBC1) protein as a key regulator of fat storage capacity of adipocytes. We found that knockout (KO) of DBC1 facilitated fat cell differentiation and lipid accumulation and increased fat storage capacity of adipocytes in vitro and in vivo. This effect resulted in a “healthy obesity” phenotype. DBC1 KO mice fed a high-fat diet, although obese, remained insulin sensitive, had lower free fatty acid in plasma, were protected against atheroscle...
Obesity-Activated Adipose-Derived Stromal Cells Promote Breast Cancer Growth and Invasion
Neoplasia
Obese women diagnosed with breast cancer have an increased risk for metastasis, and the underlying mechanisms are not well established. Within the mammary gland, adipose-derived stromal cells (ASCs) are heterogeneous cells with the capacity to differentiate into multiple mesenchymal lineages. To study the effects of obesity on ASCs, mice were fed a control diet (CD) or high-fat diet (HFD) to induce obesity, and ASCs were isolated from the mammary glands of lean and obese mice. We observed that obesity increased ASCs proliferation, decreased differentiation potential, and upregulated expression of α-smooth muscle actin, a marker of activated fibroblasts, compared to ASCs from lean mice. To determine how ASCs from obese mice impacted tumor growth, we mixed ASCs isolated from CD-or HFD-fed mice with mammary tumor cells and injected them into the mammary glands of lean mice. Tumor cells mixed with ASCs from obese mice grew significantly larger tumors and had increased invasion into surrounding adipose tissue than tumor cells mixed with control ASCs. ASCs from obese mice demonstrated enhanced tumor cell invasion in culture, a phenotype associated with increased expression of insulin-like growth factor-1 (IGF-1) and abrogated by IGF-1 neutralizing antibodies. Weight loss induced in obese mice significantly decreased expression of IGF-1 from ASCs and reduced the ability of the ASCs to induce an invasive phenotype. Together, these results suggest that obesity enhances local invasion of breast cancer cells through increased expression of IGF-1 by mammary ASCs, and weight loss may reverse this tumorpromoting phenotype.
World journal of experimental medicine, 2013
Core tip: Recent evidence has shown that the constellation of obesity, insulin resistance and adipokines is associated with the risk and prognosis of postmenopausal breast cancer (BC). Direct evidence is growing rapidly supporting the stimulating and/or inhibiting role of adipokines in the process of development and progression of BC. Recent studies support a role of adipokines as novel risk factors and potential diagnostic and prognostic biomarkers in BC. This editorial aims at providing important insight into the potential pathophysiological mechanisms linking adipokines to the etiopathogenesis of BC in the context of a dysfunctional adipose tissue and insulin resistance in obesity. Understanding of these mechanisms may be important for the development of attractive preventive and therapeutic strategies against obesity-related breast malignancy.
A literature review of Adipocyte regulation of breast cancer
A literature review of Adipocyte regulation of breast cancer
The breast neoplasm has become one of the most threat to women’s health worldwide. In developed countries, one in every eight women has been diagnosed with at least one kind of breast neoplasm during their lifetime. Annually, there are about 1.1 million women diagnosed with mammary neoplasm and approximately 410,000-508,000 women died because of this carcinoma. Obesity has been proved association with breast mammary carcinoma through the substance & hormone released by adipocytes into the metabolic system of the neoplasm and could affect the process of tumor development more severely. The mortality of obese women with breast tumor is 2.5 times higher. The World Health Organization (WHO) has redefined obesity as the pandemic not only in countries which have westernized lifestyle but in globally including developing countries because of its impacts on health particularly in some non-communicable diseases such as cancer and diabetes. Obese status is a direct result of excess size or/and the number of adipose tissues in the body which are formed by the adipocytes are also being called fatty cells have the main function of storing triglyceride. Now it is globally known that adipose tissues are not only the energy resources but also an endocrine organ that releases some substance, hormone, and cytokines into the bloodstream and changing the microenvironment of organism cells ,adipocytes could be a potential factor to lead to some type of cancers and support the metabolism of cancer and its microenvironment .There is unambiguous evidence of an association between obesity and breast neoplasm but lacking evidence of the interacting mechanism of metabolic of adipocytes with breast tumor in some points. In this paper, we will review the mechanism of adipocytes metabolic and breast tumors in development, invasion, and metastasis.
Advances in the Prevention and Treatment of Obesity-Driven Effects in Breast Cancers
Frontiers in Oncology, 2022
Obesity and associated chronic inflammation were shown to facilitate breast cancer (BC) growth and metastasis. Leptin, adiponectin, estrogen, and several pro-inflammatory cytokines are involved in the development of obesity-driven BC through the activation of multiple oncogenic and pro-inflammatory pathways. The aim of this study was to assess the reported mechanisms of obesity-induced breast carcinogenesis and effectiveness of conventional and complementary BC therapies. We screened published original articles, reviews, and meta-analyses that addressed the involvement of obesity-related signaling mechanisms in BC development, BC treatment/prevention approaches, and posttreatment complications. PubMed, Medline, eMedicine, National Library of Medicine (NLM), and ReleMed databases were used to retrieve relevant studies using a set of keywords, including "obesity," "oncogenic signaling pathways," "inflammation," "surgery," "radiotherapy," "conventional therapies," and "diet." Multiple studies indicated that effective BC treatment requires the involvement of diet-and exercise-based approaches in obese postmenopausal women. Furthermore, active lifestyle and diet-related interventions improved the patients' overall quality of life and minimized adverse side effects after traditional BC treatment, including postsurgical lymphedema, post-chemo nausea, vomiting, and fatigue. Further investigation of beneficial effects of diet and physical activity may help improve obesity-linked cancer therapies.