Role of Leptin and Adiponectin in Carcinogenesis

SIMPLE SUMMARY: The involvement of leptin and adiponectin with receptors in the formation of many types of cancer as well as their impact on the clinical course of cancer patients are well established; however, the mechanisms of action of these adipokines are difficult to understand and thus need to be clarified. This review comprehensively presents in a systematized manner the implication of leptin and adiponectin in different stages of cancer development, focusing on interactions with the tumor microenvironment and its components in addition to their impact on the epithelial–mesenchymal transition and angiogenesis. A solid insight into these mechanisms is essential for the future potential use of these adipokines in cancer diagnostics and therapeutics. 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.