Abstract
Uveal melanoma is highly metastatic, prognosis is poor and there are no effective treatments to extend survival. Accumulating evidence suggests that thyroid hormones have a mitogenic effect via binding to αvβ3 integrin. We aimed to examine the impact of thyroid status on survival in a murine B16F10 model for ocular melanoma, highly expressing the integrin. In two independent experiments oral propylthiouracil (PTU) was used to induce hypothyroidism (n=9), thyroxine to induce hyperthyroidism (n=11) and mice given plain water served as control (n=8). At day 21, the subretinal space was inoculated with 10(2) B16F10 cells. In non-inoculated mice (n=6 of each group) serum free T4 (FT4) levels were measured and additional non-inoculated mice (3 given PTU and 4 given thyroxine or water) served as internal control to demonstrate the impact of the dissolved substance. The PTU-inoculated mice showed clinical evidence of intraocular tumor growth significantly later than the thyroxine mice (P=0.003) and survival time was significantly longer (P<0.001). FT4 levels differed significantly between groups (P<0.001) and with no signs of illness in the internal control group. Our findings suggest that hyperthyroidism shortens survival, whereas relative hypothyroidism may have a protective role in metastatic ocular melanoma.
Highlights
Uveal melanoma (UM) is the most common primary intraocular malignancy in adults, and a condition that may lead to fatal metastases [1, 2]
Our findings suggest that hyperthyroidism shortens survival, whereas relative hypothyroidism may have a protective role in metastatic ocular melanoma
For in vivo testing we used the mouse melanoma B16F10 cell line, given its ability to form tumors when injected into the anterior eye chamber of murine eyes[1417]
Summary
Uveal melanoma (UM) is the most common primary intraocular malignancy in adults, and a condition that may lead to fatal metastases [1, 2]. Despite considerable improvement in local treatments, especially that of eyepreserving radiotherapy, there has been no change in survival rates in the past 4 decades [4, 6] Taken together, these poor outcomes emphasize the need for alternatives to traditional treatments for UM. One explanation for the possible association between thyroid hormone levels and cancer was recently given in the form of a receptor for L-thyroxine (T4) and 3,5,3’-triiodo-Lthyronine (T3) on plasma membrane integrin αvβ3 [10, 13]. This integrin appears to mediate the proliferative action of the hormone on blood vessel cells and on tumor cells [10]
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