Role of Leptin and Adiponectin in Carcinogenesis

Abstract

Hormones produced by adipocytes, leptin and adiponectin, are associated with the process of carcinogenesis. Both of these adipokines have well-proven oncologic potential and can affect many aspects of tumorigenesis, from initiation and primary tumor growth to metastatic progression. Involvement in the formation of cancer includes interactions with the tumor microenvironment and its components, such as tumor-associated macrophages, cancer-associated fibroblasts, extracellular matrix and matrix metalloproteinases. Furthermore, these adipokines participate in the epithelial–mesenchymal transition and connect to angiogenesis, which is critical for cancer invasiveness and cancer cell migration. In addition, an enormous amount of evidence has demonstrated that altered concentrations of these adipocyte-derived hormones and the expression of their receptors in tumors are associated with poor prognosis in various types of cancer. Therefore, leptin and adiponectin dysfunction play a prominent role in cancer and impact tumor invasion and metastasis in different ways. This review clearly and comprehensively summarizes the recent findings and presents the role of leptin and adiponectin in cancer initiation, promotion and progression, focusing on associations with the tumor microenvironment and its components as well as roles in the epithelial–mesenchymal transition and angiogenesis.

Towards Understanding the Development of Breast Cancer: The Role of RhoJ in the Obesity Microenvironment

“…In order to achieve this aim, we cultured HME1 cells, a mammalian mammary epithelial cell line in a special medium to mimic the obesity micro-environment by combining low concentrations of adiponectin and different inflammatory mediators together (leptin, adiponectin, TNF-α, IL-6, and PAI-1). To note, each of these molecules was tested separately, and their role in EMT, cancer cell migration, and invasion has been extensively studied: Leptin [75][76][77], IL-6 [78,79], TNF-α [80,81], PAI-1 [82], and adiponectin [83,84]. To our knowledge, this is the first study where all of these have been combined together with the aim of understanding the role of the obesity micro-environment regarding cancer biogenesis and development (rather than the role of one molecule or another in an isolated setting).…”

Obesity and Cancer Rehabilitation for Functional Recovery and Quality of Life in Breast Cancer Survivors: A Comprehensive Review

“…On the other hand, the tumor-specific microenvironment is a complex set of cells and molecules surrounding tumors. This system includes tumor endothelial cells, tumor stromal cells with cancer-associated fibroblasts and cancer-associated adipocytes, normal epithelial cells, immune cells with tumor-associated macrophages, signaling molecules, blood vessels, and a non-cellular part called the extracellular matrix [29]. Leptin and adiponectin play intricate roles within the tumor microenvironment.…”

“…More specifically, leptin can directly and indirectly impact on inflammation and angiogenesis, while adiponectin's role is not fully understood but appears to be related to antioxidant markers and tumor outcomes in different cancers. These adipokines contribute to the complex interplay of factors within the tumor microenvironment, potentially influencing cancer progression [29].…”

The Role of Adipokines in Tumor Progression and Its Association with Obesity

“…The leptin receptor belongs to the class I cytokine receptor family and has six splice variants. The leptin transmembrane receptor (Ob-R) isoforms (ObRa-ObRf) are divided into three classes based on their differences in length: long (ObRb), short (ObRa, ObRc, ObRd, and ObRf), and secretory (ObRe) isoforms [17]. Ob-R has an intracellular domain of sufficient length to initiate various signaling pathways that contribute to tumor cell survival, growth, and metastasis [18].…”

“…Furthermore, AMPK activation suppresses PI3K and mTOR signaling, resulting in a cytoprotective effect of adiponectin. Through suppressors of cytokine signaling 3 (SOCS3), adiponectin inhibits the activation of STAT3, which promotes the proliferation, survival, and invasion of cancer cells [17,25]. The pleiotropic functions of adiponectin include maintaining energy homeostasis; exerting anti-inflammatory actions such as inhibiting macrophages, T lymphocytes, and natural killer cells; promoting anti-apoptosis; and facilitating pro-angiogenic activities [26,27].…”