Expression and possible function of IL-2 and IL-15 receptors on human uveal melanoma cells.
OBJECTIVE
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 -15Ralpha. 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 (51)Cr-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.
He
Yu-Guang
YG
Department of Ophthalmology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9057, USA.
Mayhew
Elizabeth
E
Mellon
Jessamee
J
Niederkorn
Jerry Y
JY
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D006801:Humans; D019409:Interleukin-15 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology; D008545:Melanoma / Q000378:metabolism* / Q000503:physiopathology / Q000556:secondary; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2 / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D014604:Uveal Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology
D000970:Antineoplastic Agents; C508024:IL15RA protein, human; D019409:Interleukin-15; D007376:Interleukin-2; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins