Human melanoma cells express functional receptors for thyroid-stimulating hormone.
We have reported a high prevalence of hypothyroidism in the cutaneous melanoma population, suggesting that the pathologic hormonal environment of hypothyroidism promotes melanoma growth. The objective of this study was to test the hypothesis that TSH, which circulates at elevated levels in hypothyroid individuals, stimulates the growth of melanoma cells. Our results show that TSH receptors (TSHR) are expressed by virtually all cutaneous melanocytic lesions, including benign nevi, dysplastic nevi, and melanomas, with higher expression found in malignant and pre-malignant lesions. The finding of TSHR expression by human tumors is confirmed in cultured melanoma cells and melanocytes, in which TSHR expression is demonstrated by immunofluorescent staining, western blotting, and reverse transcriptase-PCR. Melanoma TSHR are functional, as evidenced by the ability of TSH to induce the formation of cAMP and to activate the mitogen-activated protein kinase (MAPK) pathway. Cultured melanoma cells, but not melanocytes, are induced to proliferate at a physiologically relevant concentration of TSH. Taken together, these data support the hypothesis that TSH is a growth factor for human melanoma. Our findings have broad clinical implications for the prevention of melanoma and the management of established disease.
Ellerhorst
Julie A
JA
Department of Experimental Therapeutics, Unit 362, University of Texas, MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas, USA. jaellerh@mdanderson.org
Sendi-Naderi
Aresu
A
Johnson
Marilyn K
MK
Cooke
Carolyn P
CP
Dang
Shyam M
SM
Diwan
A Hafeez
AH
D015153:Blotting, Western; D049109:Cell Proliferation; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007037:Hypothyroidism; D007124:Immunoenzyme Techniques; D008544:Melanocytes / Q000378:metabolism / Q000473:pathology; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009508:Nevus, Pigmented / Q000378:metabolism / Q000473:pathology; D016133:Polymerase Chain Reaction; D011989:Receptors, Thyrotropin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D013972:Thyrotropin / Q000378:metabolism*
D011989:Receptors, Thyrotropin; D013972:Thyrotropin; D000242:Cyclic AMP; D020928:Mitogen-Activated Protein Kinases