Promotion of melanoma growth by the metabolic hormone leptin.
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.
Ellerhorst
Julie A
JA
Department of Experimental Therapeutics, Unit 362, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. jaellerh@mdanderson.org
Diwan
A H
AH
Dang
Shyam M
SM
Uffort
Deon G
DG
Johnson
Marilyn K
MK
Cooke
Carolyn P
CP
Grimm
Elizabeth A
EA
D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D020738:Leptin / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009506:Nevus / Q000378:metabolism; D054411:Receptors, Leptin / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology
D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin; D054411:Receptors, Leptin; D020928:Mitogen-Activated Protein Kinases