The adipocyte-released
hormone-like
cytokine/
adipokine leptin behaves differently in
obesity compared to its functions in the normal healthy state. In obese individuals, elevated
leptin levels act as a pro-inflammatory
adipokine and are associated with certain types of
cancers. Further, a growing body of evidence suggests that higher circulating
leptin concentrations and/or elevated expression of
leptin receptors (Ob-R) in
tumors may be poor prognostic factors. Although the underlying pathological mechanisms of
leptin's association with poor prognosis are not clear,
leptin can impact the tumor microenvironment in several ways. For example,
leptin is associated with a number of biological components that could lead to
tumor cell invasion and distant
metastasis. This includes interactions with
carcinoma-associated fibroblasts,
tumor promoting effects of infiltrating macrophages, activation of
matrix metalloproteinases,
transforming growth factor-β signaling, etc. Recent studies also have shown that
leptin plays a role in the epithelial-mesenchymal transition, an important phenomenon for
cancer cell migration and/or
metastasis. Furthermore,
leptin's potentiating effects on
insulin-like growth factor-I,
epidermal growth factor receptor and HER2/neu have been reported. Regarding unfavorable prognosis,
leptin has been shown to influence both
adenocarcinomas and
squamous cell carcinomas. Features of poor prognosis such as
tumor invasion, lymph node involvement and distant
metastasis have been recorded in several
cancer types with higher levels of
leptin and/or Ob-R. This review will describe the current scenario in a precise manner. In general,
obesity indicates poor prognosis in
cancer patients.