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M.M. Valença Cordeiro Barbosa, A.L. Caissie, J.A. Marshall, P.L. Blanco, M.N. Burnier Jr.; The Effect of In Vitro Macrophage-Tumor Cell Interaction on the Production of Migration Inhibitory Factor (MIF) . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1559.
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Purpose: MIF is a pro-inflammatory cytokine that has been shown to be expressed in both cutaneous and uveal melanoma cell lines, as well macrophages. MIF has been associated with processes such as tumor cell proliferation and metastasis. The aim of this study is to investigate in vitro the effect of macrophage-tumor cell interaction on the production of MIF. Methods: Five human uveal melanoma cell lines of previously determined metastatic potential (MP) (92.1>SP6.5>OCM-1=UW-1>MKT-BR no MP), and one macrophage cell line (28SC) were seeded in RPMI medium. After 18 hours, RPMI diluted (20%) media from the uveal melanoma cell lines was placed on the macrophage cell line. Diluted macrophage cell line media was placed on each uveal melanoma cell line. Tumor and macrophage cells without conditioned medium were used as controls. MIF levels in the medium were determined by ELISA prior to media transfer and after 6, 12, 24, and 36 hours. Results: Without conditioned medium all cell lines express MIF at low levels (MKT-BR>OCM-1>UW-1>92.1=SP6.5>28SC). A two-fold increase in MIF expression, from 501 pg/ml to 1216 pg/ml, was found in one uveal melanoma cell line (SP6.5). A smaller increase (approximately 100 pg/ml) was found in two uveal melanoma cell lines (92.1, OCM-1) while no increase was found in MKT-BR and UW-1. A greater than two fold increase was found in macrophage MIF expression with UW-1 media, and a greater than three fold increase was found in macrophage MIF expression with media from the other four uveal melanoma cell lines. Conclusions: MIF expression is affected by the soluble factors secreted during in vitro macrophage-tumor cell interaction. The most significant increase in MIF expression was found in macrophages exposed to the conditioned medium of the tumor cells. MIF upregulation following tumor cell-macrophage interaction may explain, in part, how this interaction contributes to uveal melanoma progression.
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