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A Morilla-Grasa, MC Mendez, AL Caissie, J-CA Marshall, R Lopez, MN Burnier; The Expression of Cyclooxygenase-2 (COX-2) in an Animal Model of Primary and Metastatic Human Uveal Melanoma . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1135.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: COX-2, a prostaglandin synthetase involved in processes such as angiogenesis and invasion, has been found in various human malignancies such as skin and uveal melanoma. The objective of this study is to investigate the expression of COX-2 in the cells of primary ocular tumors and lung metastases taken from a 12 week period animal model of uveal melanoma (UM), in which immunosuppressed (Cyclosporin A) albino rabbits are injected with 5 human UM cell lines of different metastatic potential (MP)(92.1, high MP; SP6.5, high MP; OCM-1, low MP; UW-1, low MP; MKT-BR, no MP). Methods: Sixty-four eyes of 64 rabbits, injected with 92.1 cell line (18), SP6.5 cell line (20), OCM-1 cell line (8), UW-1 cell line (9) and MKT-BR cell line (7), as well as 19 lungs (9 lungs with 92.1 cell line metastasis, 8 with SP6.5 metastasis, 1 with OCM-1 metastasis and 1 with UW-1 metastasis) were obtained from the animal model. The formalin-fixed, paraffin embedded specimens were immunostained with a monoclonal antibody against COX-2. The ocular tumors were evaluated for the presence of necrosis, extra-ocular extension, tumor associated macrophages (TAM) and tumor infiltrating lymphocytes (TIL). The tumors were also classified as diffuse or nodular. Results: Two ocular tumor specimens were lost during the immunostain process. All 62 UM and all 19 lung metastases studied were negative for COX-2. Fifty-eight out of 62 (93.5%) UM had necrosis and TAM. Forty-eight out of 62 (77%) UM had extra-ocular extension. Sixty out of 62 (97%) UM had TIL. Fifty-nine out of 62 (95%) UM were classified as diffuse. Conclusion: Whereas this animal model of uveal melanoma is effective in producing metastasis (30%), it does not perfectly mimic the human disease. There was a disproportionate amount of necrosis, extra-ocular extension, and TIL. In addition, the vast majority of the ocular tumors were of a diffuse pattern, which is rare in human uveal melanomas. The lack of COX-2 expression in this animal model may be due to the dose or type of immunosuppressant (Cyclosporin A) used. Therefore the conditions of this animal model are not appropriate for studying the effect of COX-2 inhibitors on uveal melanoma and other forms of immunosuppression should be investigated for this purpose.
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