Oncotarget

Research Papers:

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 and Osnat Ashur-Fabian

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Oncotarget. 2015; 6:11038-11046. https://doi.org/10.18632/oncotarget.3566

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Abstract

Ido Didi Fabian1, Mordechai Rosner1, Ina Fabian2, Vicktoria Vishnevskia-Dai1, Ofira Zloto1, Elena Shinderman Maman3,4, Keren Cohen3,4, Martin Ellis4, Hung-Yun Lin5,6, Aleck Hercbergs7, Paul J. Davis6,8 and Osnat Ashur-Fabian3,4

1 Goldschleger Eye Institute, Sheba Medical Center, Tel Hashomer, affiliated to Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

2 Department of Cell and Developmental Biology, the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

3 Department of Human Molecular Genetics and Biochemistry, the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

4 Translational Hemato-Oncology Laboratory, The Hematology Institute and Blood Bank, Meir Medical Center, Kfar-Saba, affiliated to Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

5 Institute of Cancer Biology and Drug Discovery, School of Medical Technology, Taipei Medical University, Taipei, Taiwan

6 Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Albany, NY, USA

7 Department of Radiation Oncology, Cleveland Clinic, Cleveland, OH, USA

8 Department of Medicine, Albany Medical College, Albany, NY, USA

Correspondence to:

Ido Didi Fabian, email:

Keywords: integrin, uveal melanoma, thyroid

Received: September 23, 2014 Accepted: February 22, 2015 Published: March 14, 2015

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.


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