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

Research output: Contribution to journalArticle

16 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

Fingerprint

Thyroid Hormones
Melanoma
Propylthiouracil
Thyroxine
Hyperthyroidism
Hypothyroidism
Integrins
Water
Thyroid Gland
Control Groups
Growth
Serum
Neoplasms

Keywords

  • Integrin
  • Thyroid
  • Uveal melanoma

ASJC Scopus subject areas

  • Oncology

Cite this

Fabian, I. D., Rosner, M., Fabian, I., Vishnevskia-Dai, V., Zloto, O., Maman, E. S., ... Ashur-Fabian, O. (2015). Low thyroid hormone levels improve survival in murine model for ocular melanoma. Oncotarget, 6(13), 11038-11046.

Low thyroid hormone levels improve survival in murine model for ocular melanoma. / Fabian, Ido Didi; Rosner, Mordechai; Fabian, Ina; Vishnevskia-Dai, Vicktoria; Zloto, Ofira; Maman, Elena Shinderman; Cohen, Keren; Ellis, Martin; Lin, Hung Yun; Hercbergs, Aleck; Davis, Paul J.; Ashur-Fabian, Osnat.

In: Oncotarget, Vol. 6, No. 13, 2015, p. 11038-11046.

Research output: Contribution to journalArticle

Fabian, ID, Rosner, M, Fabian, I, Vishnevskia-Dai, V, Zloto, O, Maman, ES, Cohen, K, Ellis, M, Lin, HY, Hercbergs, A, Davis, PJ & Ashur-Fabian, O 2015, 'Low thyroid hormone levels improve survival in murine model for ocular melanoma', Oncotarget, vol. 6, no. 13, pp. 11038-11046.
Fabian ID, Rosner M, Fabian I, Vishnevskia-Dai V, Zloto O, Maman ES et al. Low thyroid hormone levels improve survival in murine model for ocular melanoma. Oncotarget. 2015;6(13):11038-11046.
Fabian, Ido Didi ; Rosner, Mordechai ; Fabian, Ina ; Vishnevskia-Dai, Vicktoria ; Zloto, Ofira ; Maman, Elena Shinderman ; Cohen, Keren ; Ellis, Martin ; Lin, Hung Yun ; Hercbergs, Aleck ; Davis, Paul J. ; Ashur-Fabian, Osnat. / Low thyroid hormone levels improve survival in murine model for ocular melanoma. In: Oncotarget. 2015 ; Vol. 6, No. 13. pp. 11038-11046.
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