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A.L. Caissie, J.A. Marshall, E. Antecka, I. Zundane, M.N. Burnier Jr.; The Effect of Conditioned Medium from COX-2 Expressing Macrophage on the In Vitro Proliferation of Uveal Melanoma Cell Lines . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1558.
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Purpose: A high number of tumor-associated macrophages (TAM) has been linked to poor prognosis in uveal melanoma. It has previously been shown that TAM express cyclooxygenase-2 (COX-2), a prostaglandin synthase linked to tumorigenic processes such as cell proliferation, migration and invasion. Macrophages, often found at the invading edge of the tumor, have been shown in vitro to inhibit proliferation while stimulating migration of colon carcinoma cell lines. This study aims to investigate the effect of conditioned medium from activated COX-2-expressing macrophages on the in vitro proliferation rate of uveal melanoma cell lines. Methods: The THP-1 human monocyte cell line was differentiated with phorbol 12-myristate 13-acetate (PMA) and stimulated with IFN-γ and LPS to express COX-2. Proliferation rates of five human melanoma cell lines (92.1, SP6.5, MKT-BR, OCM-1 and UW-1) were assayed in triplicate using the tritiated thymidine uptake (TTU) method. TTU results were obtained for cell lines seeded in RPMI medium as well as RPMI medium with interferon-gamma (IFN-γ) and lipopolysaccharide (LPS). These TTU results were compared to results from cell lines seeded in 24 hour conditioned medium from COX-2 expressing macrophages. Results: TTU showed that the rate of tumor cell proliferation was decreased by conditioned medium from activated macrophage. In each cell line, this decrease in proliferation was at least two times greater than that observed in tumor cells with non-conditioned IFN-γ and LPS medium. Conclusions: Conditioned medium from activated COX-2 expressing macrophages decreased the proliferation rate of all uveal melanoma cell lines. COX-2 expressing macrophages in uveal melanoma may inhibit tumor cell proliferation while enhancing other neoplastic properties such as migration and invasion. The mechanisms behind this decrease in proliferation should be investigated further.
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