Human melanoma cells express functional receptors for thyroid-stimulating hormone

Abstract

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 premalignant 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 mitogenactivated 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.

False Positive Result in the Whole-Body Scan with 131-I in the Follow-up of Differentiated Thyroid Cancer: The Fistula Tract Accompanied by the Suture Granuloma

“…According to Ellerhost et al results, TSH receptors are expressed by almost all cutaneous melanocytic lesions, including benign nevi, dysplastic nevi, and melanomas. In addition, higher expression is observed in malignant and pre-malignant lesions (12). We report here a newly identified cause of false-positive diagnostic WBS findings with low Tg level: Fistula tract accompanying the SG.…”

Cutaneous Malignant Melanoma Associated with Papillary Thyroid Cancer

“…Continuous monitoring of the thyroid function in melanoma patients is required because hypothyroidism can worsen due to malignant melanoma and this probably is associated with thyroid carcinoma, like in our case 2,5 .…”

“…Some studies have reported that TSH is more likely to be expressed by dysplastic nevi than by benign nevi, and the dysplastic nevi of melanoma patients have a higher TSH expression than that of healthy individuals. Thus, TSH has been implicated in the malignant transformation of melanocytes to melanoma, and TSH stimulates the growth of melanoma cells 5,6 . On the other hand, the possibility has been suggested that the melanoma induces the thyroid dysfunction and this leads to hypothyroidism under the condition of low circulating thyroid hormone levels and concomitantly elevated TSH levels, although an autoimmune mechanism has also been suggested 2 .…”

TSH-induced gene expression involves regulation of self-renewal and differentiation-related genes in human bone marrow-derived mesenchymal stem cells

“…It is very well known that stimulation of TSHR by TSH results eventually in production of THs, T 3 and T 4 in thyroid cells (Toccafondi et al 1982, Szkudlinski et al 2002. However, we also know that TSHR can be expressed by extrathyroidal tissues or cells (Haraguchi et al 1996, Hoermann 1996, Dutton et al 1997, Bell et al 2000, Agretti et al 2002, Tsai et al 2004, Ellerhorst et al 2006. For example, kidney cells were shown to express a functional TSHR that transmitted signals through cAMP (Sellitti et al 2000).…”

“…Stimulation of the TSHR via TSH on thyroid cells leads to production of the thyroid hormones (THs), tri-iodothyronine (T 3 ) and thyroxine (T 4 ) (Toccafondi et al 1982). The TSHR expression by other tissue cells has also been reported (Haraguchi et al 1996, Hoermann 1996, Dutton et al 1997, Bell et al 2000, Agretti et al 2002, Tsai et al 2004, Ellerhorst et al 2006. However, exact function of its expression in extrathyroidal tissues has not been clarified.…”