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Shuo You, Qing Zhang, john lattier, Hua Yang, shin kang, Hans E Grossniklaus; Metastatic Ocular Melanoma to the Liver Exhibits Infiltrative and Nodular Growth Patterns in Mouse Models. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4113.
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© ARVO (1962-2015); The Authors (2016-present)
To evaluate the histological growth patterns and stages of these patterns of metastatic melanoma to the liver in mouse models, which are similar to patterns of metastatic ocular melanoma to the liver in humans.
Mouse melanoma cell line B16LS9 and human uveal melanoma Mel290 cells were cultured, and inoculated into the superchoroidal space in the right eyes of C57BL6, PEDF, and Nu:Nu mice, respectively, via a trans-scleral technique. The tumor-burden eyes were enucleated at the 7th day to determine primary tumor growth, and the livers were collected at the different time points to determine the hepatic metastases. Histological examination and immunohistochemical staining were then performed. All experiments were conducted according to the Association for Research in Vision and Ophthalmology statement for the use of animals in ophthalmic and vision research.
Metastases occurred in the livers of all mice. These include Stage 1 metastases (defined as tumor clusters <50 μm in diameter), stage 2 metastases (defined as tumors measuring 50-200 μm in diameter), and stage 3 metastases (defined as tumors measuring >200 μm in diameter). Immunohistochemical stains were positive for S100 or HMB45 in all tumors. Overall, stage 1 metastases out-numbered stage 2 metastases, which out-numbered stage 3 metastases (P<0.001 and P<0.005, respectively). Two patterns of metastatic growth were detected: the infiltrative pattern, where colonies from in the sinusoidal spaces of the lobule, or the nodular pattern of colonies from adjacent to the nodular venule. Mel290 in Nu:Nu mice predominantly exhibited a infiltrative growth pattern of metastasis. B16LS9 in PEDF KO mice predominantly showed a nodular pattern of growth, whereas wild-type C57BL6 mice showed both pattern of growth with equal distribution (P<0.05). The mean vascular density in stage 3 was greater than stage 2 metastases (P<0.01), with no vascularity detected in stage 1. Mean vascular density was highest in nodular pattern of growth from mice lacking PEDF.
The in vivo mouse models of human uveal melanoma is reliable and reproducible, and forms hepatic metastases which can be categorized as stage 1, 2, 3, as in humans. The infiltrative pattern in Nu:Nu mice may be due to lack of immune cells in the sinusoidal space. In contrast, the nodular pattern seen in PEDF KO may be due to increased tumor angiogenesis.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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