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Modeling the Behavior of Uveal Melanoma in the Liver

¹From the Department of Pathology, the ²Virtual Reality in Medicine Laboratory, Department of Biomedical and Health Information Sciences, and the ⁴Department of Mathematics, Statistics, and Computer Science, University of Illinois at Chicago, Chicago, Illinois; and the ³Immunology Laboratory for Tumor Diagnosis and the ⁵Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

PURPOSE. To model the behavior of uveal melanoma in the liver.

METHODS. A 15-µL suspension of metastatic MUM2B or either primary OCM1 or M619 uveal melanoma cells was injected into the liver parenchyma of 105 CB17 SCID mice through a 1-cm abdominal incision. Animals were killed at 2, 4, 6, or 8 weeks after injection. Before euthanatization, 3% FITC-BSA buffer was injected into the retro-orbital plexus of one eye of three mice. Liver tissues were examined by light and fluorescence microscopy, and were stained with human anti-laminin. Vasculogenic mimicry patterns were reconstructed from serial laser scanning confocal microscopic stacks.

RESULTS. OCM1a cells formed microscopic nodules in the mouse liver within 2 weeks after injection and metastasized to the lung 6 weeks later. By contrast, M619 and MUM2B cells formed expansile nodules in the liver within 2 weeks and gave rise to pulmonary metastases within 4 weeks after injection. Vasculogenic mimicry patterns, composed of human laminin and identical with those in human primary and metastatic uveal melanomas, were detected in the animal model. The detection of human rather than mouse laminin in the vasculogenic mimicry patterns in this model demonstrates that these patterns were of tumor cell origin and were not co-opted from the mouse liver microenvironment.

CONCLUSIONS. There are currently no effective treatments for metastatic uveal melanoma. This direct-injection model focuses on critical interactions between the tumor cell and the liver. It provides for translationally relevant approaches to the development of new modalities to detect small tumor burdens in patients, to study the biology of clinical dormancy of metastatic disease in uveal melanoma, to design and test novel treatments to prevent the emergence of clinically manifest liver metastases after dormancy, and to treat established uveal melanoma metastases.

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				V. Barak, S. Frenkel, K. Valyi-Nagy, L. Leach, M. A. Apushkin, A. Y. Lin, I. Kalickman, N. A. Baumann, J. Pe'er, A. J. Maniotis, et al. Using the Direct-Injection Model of Early Uveal Melanoma Hepatic Metastasis to Identify TPS as a Potentially Useful Serum Biomarker Invest. Ophthalmol. Vis. Sci., October 1, 2007; 48(10): 4399 - 4402. [Abstract] [Full Text] [PDF]