Relationship between natural killer cell susceptibility and metastasis of human uveal melanoma cells in a murine model

Abstract

Purpose: The purpose of this study was to determine the susceptibility of human uveal melanoma cells to in vitro and in vivo natural killer (NK) cell-mediated cytolysis and to determine if NK cells influence metastasis from the eye.

Methods: Four human uveal melanoma cell lines and one melanoma cell line derived from a metastatic lesion from a patient with uveal melanoma were tested for in vitro and in vivo NK cell-mediated lysis in a mouse model. Major histocompatibility complex (MHC) class I antigen expression was evaluated by flow cytometry. The role of NK cells in controlling the metastasis of uveal melanoma cells from the eye to the liver was examined in nude mice.

Results: Sensitivity to in vitro and in vivo lysis by human and murine NK cells was correlated with reduced expression of MHC class I antigens. Uveal melanoma lines expressing normal MHC class I antigen expression were insensitive to NK cell-mediated lysis, both in vitro and in vivo. Metastasis of uveal melanoma cells was inhibited by NK cell activity because disruption of in vivo NK function produced a sharp increase in the spontaneous metastasis of intraocular melanomas in nude mice.

Conclusions: There is considerable variation in the susceptibility of human uveal melanomas to NK cell-mediated cytolysis. Susceptibility is closely correlated with reduced expression of MHC class I antigen expression. Disruption of NK cell function significantly increases the development of hepatic metastases from human uveal melanoma cells.