Syed N A, Windle J J, Darjatmoko S R, Lokken J M, Steeves R A, Chappell R, Wallow I H, Koop B A, Mangold G, Howes K A, Albert D M
Department of Ophthalmology, University of Pennsylvania, Philadelphia, USA.
Invest Ophthalmol Vis Sci. 1998 Dec;39(13):2800-5.
To describe the cell of origin, tumor progression, light and electron microscopic appearance, immunohistochemical properties, and response to frequently used anticancer therapies in two transgenic models of intraocular melanoma.
Two lines of transgenic mice that develop pigmented intraocular tumors were produced with the SV40 T and t antigens under the control of the mouse tyrosinase gene. Tumors were sequentially studied and characterized by light microscopy, electron microscopy, and immunohistochemistry stains. Tumor response to two cycles of dacarbazine was assessed on the basis of tumor size in one group of animals. Response to external beam irradiation was measured by survival time in other animals.
Two lines of transgenic mice developed bilateral intraocular tumors with complete penetrance and without primary cutaneous melanomas. Tumors developed first in the retinal pigment epithelial layer, with subsequent retinal and choroidal invasion, extraocular extension, and metastasis. Tumors stained positive for S-100, HMB-45, and Fas-ligand. Electron microscopy revealed polarization of tumor cells with basement membrane formation, microvilli, immature melanosomes, and abundant endoplasmic reticulum. Dacarbazine significantly reduced tumor size in these mice, and a trend toward dose-dependent decrease in survival was found with external beam irradiation.
Tumors developed from the retinal pigment epithelium. Their histology and growth, however, closely resembled that of human choroidal melanoma. This model may be a useful tool for future studies of endogenous primary pigmented tumors limited to the eye. Response to standard therapies suggests it can serve as a model with which to evaluate therapeutic modalities.
描述两种眼内黑色素瘤转基因模型中的肿瘤起源细胞、肿瘤进展、光镜和电镜表现、免疫组化特性以及对常用抗癌疗法的反应。
利用小鼠酪氨酸酶基因控制下的SV40 T抗原和t抗原，培育出两系发生色素性眼内肿瘤的转基因小鼠。通过光镜、电镜和免疫组化染色对肿瘤进行序贯研究和特征描述。在一组动物中，根据肿瘤大小评估达卡巴嗪两个周期治疗后的肿瘤反应。在其他动物中，通过生存时间测量外照射的反应。
两系转基因小鼠发生双侧眼内肿瘤，具有完全的穿透性且无原发性皮肤黑色素瘤。肿瘤首先在视网膜色素上皮层发生，随后侵犯视网膜和脉络膜，向眼外扩展并发生转移。肿瘤S-100、HMB-45和Fas配体染色呈阳性。电镜显示肿瘤细胞极化，有基底膜形成、微绒毛、未成熟黑素小体和丰富的内质网。达卡巴嗪显著减小了这些小鼠的肿瘤大小，外照射后发现生存有剂量依赖性下降趋势。
肿瘤起源于视网膜色素上皮。然而，其组织学和生长情况与人类脉络膜黑色素瘤极为相似。该模型可能是未来研究仅限于眼部的内源性原发性色素性肿瘤的有用工具。对标准疗法的反应表明它可作为评估治疗方式的模型。
