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Y-G He, E Mayhew, JY Niederkorn; Expression and Function of IL-2 Receptor on Human Uveal Melanoma Cells . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2215.
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Purpose: The presence of tumor-infiltrating lymphocytes (TIL) has been correlated with a poor prognosis in uveal melanoma patients. One potential explanation for this paradox is possibility that TIL secrete growth factors that stimulate the proliferation of melanoma cells in situ. Since interleukin-2 receptors (IL-2R) have been detected on some murine neoplasms, we examined human uveal melanomas for the expression of IL-2R and the effect of exogenous IL-2 on the proliferation of IL-2R+ melanoma cells. Methods: Nine human uveal melanoma cell lines, including two cell lines from uveal melanoma metastases were tested by flow cytometry for the expression of human IL-2R (CD25). Melanoma cells were cultured in the presence of various concentrations of recombinant human IL-2 (100, 500, and 1,000 u/ml) for 24, 48, and 72 hr. Cell proliferation was determined by tritiated thymidine uptake and IL-2R expression was assessed by flow cytometry. Results: All of the uveal melanoma and metastases cell lines tested demonstrated at least some level of IL-2R expression that was above the negative control cells (Chang human liver cell line). In seven of the nine uveal melanoma cell lines and in both of the metastasis cell lines, IL-2 induced a 3 to 8 fold upregulation of IL-2R expression (P<0.05) compared to untreated controls. Although IL-2 did not affect the proliferation of six of the nine uveal melanoma cell lines, it did induce a 45-68% increase in the proliferation of both metastatic cell lines. Conclusion: Human uveal melanoma cells express low levels of IL-2R that can be upregulated by the T cell cytokine, IL-2. Although only two metastases cell lines were tested, the results suggest that IL-2 by TIL might affect the malignant behavior of a primary uveal melanoma by stimulating the proliferation of subpopulations of metastatic cells within the primary neoplasm.
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