Schiffner Susanne, Braunger Barbara M, de Jel Miriam M, Coupland Sarah E, Tamm Ernst R, Bosserhoff Anja K
University of Regensburg, Institute of Pathology, Molecular Pathology, Franz-Joseph-Strauss-Allee 11, 93053 Regensburg, Germany.
University of Regensburg, Institute of Human Anatomy and Embryology, Universitaetsstraße 31, 93053 Regensburg, Germany.
Exp Eye Res. 2014 Oct;127:59-68. doi: 10.1016/j.exer.2014.07.009. Epub 2014 Jul 19.
Although rare, uveal melanoma (UM) is the most common primary intraocular tumor in adults. About half of UM patients develop metastatic disease typically in the liver and die within a short period, due to ineffective systemic therapies. UM has unique and distinct genetic features predictive of metastasis. Animal models are required to improve our understanding of therapeutic options in disseminated UM. Since spontaneous murine UM models are lacking, our aim was to analyze the suitability of the established transgenic melanoma mouse model Tg(Grm1) as a new UM model system. We demonstrated that adult Grm1 transgenic mice develop choroidal thickening and uveal melanocytic neoplasia with expression of the melanocytic markers S100B and MelanA. Further, we showed that GRM1 is expressed in human UM, similar to skin melanoma. This study presents a new mouse model for spontaneous UM and suggests that the glutamate signaling pathway is a possible target for UM therapy.
尽管葡萄膜黑色素瘤（UM）较为罕见，但它是成人最常见的原发性眼内肿瘤。由于全身治疗无效，约一半的UM患者会发生转移性疾病，通常转移至肝脏，并在短时间内死亡。UM具有独特且明显的预测转移的基因特征。需要动物模型来增进我们对播散性UM治疗选择的理解。由于缺乏自发的小鼠UM模型，我们的目的是分析已建立的转基因黑色素瘤小鼠模型Tg(Grm1)作为一种新的UM模型系统的适用性。我们证明成年Grm1转基因小鼠出现脉络膜增厚和葡萄膜黑素细胞肿瘤形成，并表达黑素细胞标志物S100B和MelanA。此外，我们表明GRM1在人类UM中表达，类似于皮肤黑色素瘤。本研究提出了一种新的自发性UM小鼠模型，并表明谷氨酸信号通路可能是UM治疗的一个靶点。
