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Simona Luise Schlereth, Sandra Iden, Melina Mescher, Konrad R Koch, Claus Cursiefen, Ludwig M. Heindl; New mouse model for conjunctival melanoma. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5438.
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Conjunctival melanoma is a rare but potentially aggressive ocular cancer, affecting about 0.8 patients per million with a mortality rate of 7-24% in five years. By now, there are no published mouse models to study this malignancy. In this study we investigate a new mouse model for conjunctival melanoma.
Female 6-8 weeks old black six mice were subconjunctivally injected with different doses of 384-HGF+Cdk4 tumor cells (3 groups - first group: 1x106 cells, second: 5x105, third: 1x105 cells). These tumor cells were isolated from dermal melanoma of HGF-Cdk4 mice. We tested different doses and documented findings by a clinical score (including redness, chemosis and tearing in a grade 0 (not detectable) to 3 (severe) and exophthalmos (yes/no)). After development of macroscopically detectable conjunctival tumor, mice were sacrificed and immunohistochemical staining was performed in liver, lymph nodes, spleen and bulbus including the conjunctiva for hematoxylin&eosin and different tumor markers (including Ki67, TRP1). Mice were inspected for macroscopically visible tumors on the skin and the lung.
Conjunctival melanoma was inducible in all mice receiving 1x106 (group1) or 5x105 HGF+cells (group 2) after only 3 days, by darkly pigmented conjunctival swelling. Experiments had to be stopped at day nine due to unilateral exophthalmos in 83% of the animals. The exophthalmos was induced by complete infiltration of tumor mass into the retroorbital space. Mice that received 1x105 HGF+cells (group 3) did not develop any clinical alterations of the eye in an observation period of 40 days. Immunohistochemistry showed intense Ki67 and TRP1 positivity within the conjunctival melanoma, even higher than in isolated in vitro cells. Ki67 expression was elevated in the draining lymphnode.
Injection of HGF+ cutaneous melanoma cells into the conjunctiva imitates a solid tumor growth within the conjunctiva and may be used as a new mouse model for a better understanding and treatment of conjunctival melanoma.
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