Low thyroid hormone levels improve survival in murine model for ocular melanoma

Ido Didi Fabian, Mordechai Rosner, Ina Fabian, Vicktoria Vishnevskia-Dai, Ofira Zloto, Elena Shinderman Maman, Keren Cohen, Martin Ellis, Hung Yun Lin, Aleck Hercbergs, Paul J. Davis, Osnat Ashur-Fabian

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20 Citations (Scopus)

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 102 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.

Original languageEnglish
Pages (from-to)11038-11046
Number of pages9
JournalOncotarget
Volume6
Issue number13
Publication statusPublished - 2015

Keywords

  • Integrin
  • Thyroid
  • Uveal melanoma

ASJC Scopus subject areas

  • Oncology

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  • Cite this

    Fabian, I. D., Rosner, M., Fabian, I., Vishnevskia-Dai, V., Zloto, O., Maman, E. S., Cohen, K., Ellis, M., Lin, H. Y., Hercbergs, A., Davis, P. J., & Ashur-Fabian, O. (2015). Low thyroid hormone levels improve survival in murine model for ocular melanoma. Oncotarget, 6(13), 11038-11046.