Adipocytes: active facilitators in epithelial ovarian cancer progression?
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Adipocytes: active facilitators in epithelial ovarian cancer progression? Lan Dai1,2*, Keqi Song1,2 and Wen Di1,2,3*
Abstract There is growing evidence that adipocytes play important roles in the progression of multiple cancers. Moreover, in obesity, adipocytes alter their original functions and contribute to the metabolic and inflammatory changes of adipose tissue microenvironment, which can further enhance tumor development. At present, the roles of adipocytes in the pathogenesis of epithelial ovarian cancer (EOC) are far from being fully elucidated. Herein, we summarized the recent advances in understanding the roles of adipocytes in EOC progression. Adipocytes, close neighbors of EOC tissue, promote EOC growth, invasion, metastasis and angiogenesis through adipokine secretion, metabolic remodeling and immune microenvironment modulation. Moreover, adipocytes are important therapeutic targets and may work as useful anticancer drug delivery depot for EOC treatment. Furthermore, adipocytes also act as a therapeutic obstacle for their involvement in EOC treatment resistance. Hence, better characterization of the adipocytes in EOC microenvironment and the crosstalk between adipocytes and EOC cells may provide insights into EOC progression and suggest novel therapeutic opportunities. Keywords: Epithelial ovarian cancer, Adipocytes, Cancer progression
Introduction Adipose tissue, the main part of human body, is found mainly under the skin but also in deposits such as muscles, intestines, omentum and bone marrow. For a long time, adipocytes, the major components of adipose tissue, were considered as simple depots to store and provide energy. However, since the discovery of adipocyte hormone leptin in 1994 [1], more than 400 adipocytesecreted factors have been found and adipocytes have now also been regarded as a main source of various endocrine and paracrine factors [2]. These adipocyte secreted products, known as “adipokines” (also called adipocytokines), include hormones (e.g. leptin, adiponectin and resistin), inflammatory cytokines [e.g. tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-8], enzymes [e.g. 17β-hydroxysteroid dehydrogenase * Correspondence: [email protected]; [email protected] 1 Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China Full list of author information is available at the end of the article
(17βHSD) and 11βHSD1], and other factors [3]. Many adipokines, such as leptin, IL-6 and IL-8, have been found to promote the growth, metastasis and drug resistance of different types of tumor [4, 5]. Accordingly, it is tempting to speculate that adipose tissue microenvironment (ATME) may be favorable for tumor progression. Obesity, a pathological condition accompanied by an excessive growth of adipose tissue, is increasing worldwide, and there is growing evidence for a link between obesity and cancer [6, 7]. This association is partly driven by ATME evolution induced by obesity. During weight gain,
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