Tetrac Delayed the Onset of Ocular Melanoma in an Orthotopic Mouse Model

Frontiers in Endocrinology

Paul J. Davis¹  Ina Fabian²  Galya Tsarfaty³  Aleck Hercbergs⁵  David M. Steinberg⁶  Ofira Zloto⁷  Ido Didi Fabian⁷  Martin Ellis⁹  Osnat Ashur-Fabian^1,10 

[1] 0Department of Medicine, Albany Medical College, Albany, NY, United States;Department of Cell and Developmental Biology, The Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel;Department of Diagnostic Imaging, Sheba Medical Center, Ramat Gan, Israel;Department of Human Molecular Genetics and Biochemistry, The Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel;Department of Radiation Oncology, Cleveland Clinic, Cleveland, OH, United States;Department of Statistics and Operations Research, Tel Aviv University, Tel Aviv, Israel;Goldschleger Eye Institute, Sheba Medical Center, Affiliated to The Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel;Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Albany, NY, United States;Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel;Translational Hemato-Oncology Laboratory, Meir Medical Center, The Hematology Institute and Blood Bank, Kfar-Saba, Israel;

关键词: melanoma;    mouse;    αvβ3 integrin;    thyroid;    tetrac;   

DOI  :  10.3389/fendo.2018.00775

来源: DOAJ

【 摘 要 】

Ocular melanoma research, the most common primary intraocular malignancy in adults, is hindered by limited in vivo models. In a series of experiments using melanoma cells injected intraocularly into mouse eyes, we developed a model for ocular melanoma. Inoculation of 5 × 105 B16F10 cells led to rapid tumor growth, extensive lung metastasis, and limited animal survival, while injection of 102 cells was sufficient for intraocular tumors to grow with extended survival. In order to improve tumor visualization, 102 melanoma cells (B16F10 or B16LS9) were inoculated into Balb/C albino mouse eyes. These mice developed intraocular tumors that did not metastasize and exhibited extended survival. Next, we studied the therapeutic potential of inhibitor of the thyroid hormones-αvβ3 integrin signaling pathway in ocular melanoma. By utilizing tetraiodothyroacetic acid (tetrac), a thyroid hormone derivative, a delay in tumor onset in the B16F10 (integrin+) arm was observed, compared to the untreated group, while in the B16LS9 cells (integrin–) a similar rate of tumor onset was noticed in both experimental and control groups. In summary, following an optimization process, the mouse ocular melanoma model was developed. The models exhibited an extended therapeutic window and can be utilized as a platform for investigating various drugs and other treatment modalities.

【 授权许可】

Unknown