Expression and possible function of IL-2 and IL-15 receptors on human uveal melanoma cells

Yu Guang He, Elizabeth Mayhew, Jessamee Mellon, Jerry Y. Niederkorn

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

PURPOSE. Interleukin-2 (IL-2) and IL-15 receptors have been detected on some murine neoplasms. Accordingly, the expression of these receptors on human uveal melanoma cell lines was examined, and the effect of exogenous IL-2 and -15 on melanoma cell proliferation, susceptibility to natural killer (NK) cell-mediated cytolysis, and sensitivity to apoptosis were assessed. METHODS. Nine human uveal melanoma cell lines and three cell lines from uveal melanoma metastases were tested by flow cytometry for the expression of human IL-2R and -15Rα. Melanoma cells were cultured, with or without recombinant human IL-2 or -15, cell proliferation was determined by tritiated thymidine incorporation, and IL-2 and -15 receptor expression was assessed by flow cytometry. The effect of these cytokines on NK activity was evaluated with a standard 51Cr-release assay. RESULTS. All the melanoma cell lines expressed IL-2R and -15R. IL-2 induced a three- to eightfold upregulation of IL-2R expression in all the melanoma cell lines. Although IL-2 did not affect the proliferation of six of the seven uveal melanoma cell lines, it induced a 32% and 57% increase in the proliferation of both metastatic cell lines. IL-15 induced proliferation on all tested cell lines (4%-68%). Both IL-2 and -15 reduced melanoma cell sensitivity to NK-cell-mediated cytolysis and cisplatin-induced apoptosis. CONCLUSIONS. The results suggest that IL-2 and -15 elaborated by tumor-infiltrating lymphocytes and macrophages may affect the malignant behavior of human uveal melanoma by stimulating proliferation and reducing uveal melanoma cell susceptibility to NK-cell-mediated cytolysis and cisplatin-induced apoptosis.

Original languageEnglish (US)
Pages (from-to)4240-4246
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Volume45
Issue number12
DOIs
StatePublished - Dec 2004

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Interleukin-15 Receptors
Interleukin-2
Cell Line
Interleukin-15
Melanoma
Natural Killer Cells
Apoptosis
Cisplatin
Flow Cytometry
Cell Proliferation
Tumor-Infiltrating Lymphocytes
Uveal melanoma
Interleukin-2 Receptors
Thymidine
Cultured Cells
Up-Regulation
Macrophages
Cytokines
Neoplasm Metastasis

ASJC Scopus subject areas

  • Ophthalmology

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Expression and possible function of IL-2 and IL-15 receptors on human uveal melanoma cells. / He, Yu Guang; Mayhew, Elizabeth; Mellon, Jessamee; Niederkorn, Jerry Y.

In: Investigative Ophthalmology and Visual Science, Vol. 45, No. 12, 12.2004, p. 4240-4246.

Research output: Contribution to journalArticle

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abstract = "PURPOSE. Interleukin-2 (IL-2) and IL-15 receptors have been detected on some murine neoplasms. Accordingly, the expression of these receptors on human uveal melanoma cell lines was examined, and the effect of exogenous IL-2 and -15 on melanoma cell proliferation, susceptibility to natural killer (NK) cell-mediated cytolysis, and sensitivity to apoptosis were assessed. METHODS. Nine human uveal melanoma cell lines and three cell lines from uveal melanoma metastases were tested by flow cytometry for the expression of human IL-2R and -15Rα. Melanoma cells were cultured, with or without recombinant human IL-2 or -15, cell proliferation was determined by tritiated thymidine incorporation, and IL-2 and -15 receptor expression was assessed by flow cytometry. The effect of these cytokines on NK activity was evaluated with a standard 51Cr-release assay. RESULTS. All the melanoma cell lines expressed IL-2R and -15R. IL-2 induced a three- to eightfold upregulation of IL-2R expression in all the melanoma cell lines. Although IL-2 did not affect the proliferation of six of the seven uveal melanoma cell lines, it induced a 32{\%} and 57{\%} increase in the proliferation of both metastatic cell lines. IL-15 induced proliferation on all tested cell lines (4{\%}-68{\%}). Both IL-2 and -15 reduced melanoma cell sensitivity to NK-cell-mediated cytolysis and cisplatin-induced apoptosis. CONCLUSIONS. The results suggest that IL-2 and -15 elaborated by tumor-infiltrating lymphocytes and macrophages may affect the malignant behavior of human uveal melanoma by stimulating proliferation and reducing uveal melanoma cell susceptibility to NK-cell-mediated cytolysis and cisplatin-induced apoptosis.",
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N2 - PURPOSE. Interleukin-2 (IL-2) and IL-15 receptors have been detected on some murine neoplasms. Accordingly, the expression of these receptors on human uveal melanoma cell lines was examined, and the effect of exogenous IL-2 and -15 on melanoma cell proliferation, susceptibility to natural killer (NK) cell-mediated cytolysis, and sensitivity to apoptosis were assessed. METHODS. Nine human uveal melanoma cell lines and three cell lines from uveal melanoma metastases were tested by flow cytometry for the expression of human IL-2R and -15Rα. Melanoma cells were cultured, with or without recombinant human IL-2 or -15, cell proliferation was determined by tritiated thymidine incorporation, and IL-2 and -15 receptor expression was assessed by flow cytometry. The effect of these cytokines on NK activity was evaluated with a standard 51Cr-release assay. RESULTS. All the melanoma cell lines expressed IL-2R and -15R. IL-2 induced a three- to eightfold upregulation of IL-2R expression in all the melanoma cell lines. Although IL-2 did not affect the proliferation of six of the seven uveal melanoma cell lines, it induced a 32% and 57% increase in the proliferation of both metastatic cell lines. IL-15 induced proliferation on all tested cell lines (4%-68%). Both IL-2 and -15 reduced melanoma cell sensitivity to NK-cell-mediated cytolysis and cisplatin-induced apoptosis. CONCLUSIONS. The results suggest that IL-2 and -15 elaborated by tumor-infiltrating lymphocytes and macrophages may affect the malignant behavior of human uveal melanoma by stimulating proliferation and reducing uveal melanoma cell susceptibility to NK-cell-mediated cytolysis and cisplatin-induced apoptosis.

AB - PURPOSE. Interleukin-2 (IL-2) and IL-15 receptors have been detected on some murine neoplasms. Accordingly, the expression of these receptors on human uveal melanoma cell lines was examined, and the effect of exogenous IL-2 and -15 on melanoma cell proliferation, susceptibility to natural killer (NK) cell-mediated cytolysis, and sensitivity to apoptosis were assessed. METHODS. Nine human uveal melanoma cell lines and three cell lines from uveal melanoma metastases were tested by flow cytometry for the expression of human IL-2R and -15Rα. Melanoma cells were cultured, with or without recombinant human IL-2 or -15, cell proliferation was determined by tritiated thymidine incorporation, and IL-2 and -15 receptor expression was assessed by flow cytometry. The effect of these cytokines on NK activity was evaluated with a standard 51Cr-release assay. RESULTS. All the melanoma cell lines expressed IL-2R and -15R. IL-2 induced a three- to eightfold upregulation of IL-2R expression in all the melanoma cell lines. Although IL-2 did not affect the proliferation of six of the seven uveal melanoma cell lines, it induced a 32% and 57% increase in the proliferation of both metastatic cell lines. IL-15 induced proliferation on all tested cell lines (4%-68%). Both IL-2 and -15 reduced melanoma cell sensitivity to NK-cell-mediated cytolysis and cisplatin-induced apoptosis. CONCLUSIONS. The results suggest that IL-2 and -15 elaborated by tumor-infiltrating lymphocytes and macrophages may affect the malignant behavior of human uveal melanoma by stimulating proliferation and reducing uveal melanoma cell susceptibility to NK-cell-mediated cytolysis and cisplatin-induced apoptosis.

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