Promotion of melanoma growth by the metabolic hormone leptin

Abstract

We have previously shown that melanoma cells proliferate in response to the metabolic hormones TRH and TSH. The objective of the present study was to test the hypothesis that a third metabolic hormone, leptin, serves as a growth factor for melanoma. Using western blotting, indirect immunofluorescence, and RT-PCR, leptin receptors were found to be expressed by human melanoma cells. In contrast, cultured melanocytes expressed message for the receptor without detectable protein. Melanoma cells responded to treatment with leptin by activating the MAPK pathway and proliferating. Melanoma cells but not melanocytes, also expressed leptin protein, creating a potential autocrine loop. Examination of human melanoma tumors by immunohistochemistry revealed that melanomas and nevi expressed leptin at a high frequency. Melanomas also strongly expressed the leptin receptor, whereas nevi expressed this receptor to a much lesser degree. We conclude that leptin is a melanoma growth factor and that a leptin autocrine-loop may contribute to the uncontrolled proliferation of these cells.

Oncogenic role and therapeutic target of leptin signaling in breast cancer and cancer stem cells

“…However, no supporting or conflicting data on these earlier results on bladder cancer have been published to date. In the case of human breast cancer [52], ovarian cancer [53], prostate cancer [54] and skin melanoma [55], leptin was overexpressed in more than 80% cases of malignant tissues determined by immunohistochemistry techniques. In brain [56], breast [52], esophagus cancers [57], Ob-R was also overexpressed in more than 80% cases of malignant tissues according to immunohistochemistry results.…”

Introduction

“…Expression of the TSH-R protein was detected in a wide panel of melanocytic lesions including melanoma. TSH activated the mitogen-activated protein kinase (MAPK) pathway and stimulated proliferation of melanoma cells, however, not melanocytes (Ellerhorst et al, 2010). Furthermore, TRH at low concentrations stimulated melanoma growth but not melanocytes’ proliferation and its expression was increased in dysplastic nevi in contrast to benign nevi and was expressed in 63% of melanoma samples (Ellerhorst et al, 2006).…”

Subcutaneous Adipocytes Promote Melanoma Cell Growth by Activating the Akt Signaling Pathway

“…It is worth noting that epidemiological studies showed a positive correlation between obesity and melanoma incidence (16,17). Mouse melanoma models also showed that obesity promoted melanoma development and progression (18,19). Many factors may contribute to the effects of obesity on melanoma growth.…”