Role of Fas ligand in uveal melanoma-induced liver damage

Background: Uveal melanoma, the most common adult intraocular malignancy, metastasizes preferentially to the liver. Areas of cell death surrounding uveal melanoma metastases were observed in the livers of mice. We hypothesized that uveal melanoma cells might express Fas ligand (FasL), facilitating FasL-mediated apoptosis of Fas-expressing hepatocytes. Purpose: To determine whether Fas ligand (FasL)-expressing human uveal melanoma cells induce apoptosis of human hepatocytes in vitro and in vivo. Methods: Human uveal melanoma cell lines were assayed for FasL expression by flow cytometry and immunohistology. A human hepatocyte cell line was assayed for Fas expression by flow cytometry. Apoptosis of hepatocytes was detected by annexin V staining in vitro, and terminal deoxynucleotidyl transferase nick end labeling (TUNEL) in vivo. Results: Human uveal melanoma cell lines expressed FasL, as determined by flow cytometry and immunohistology. Human hepatocytes were Fas-positive by flow cytometry. In vitro, annexin V staining revealed that human uveal melanoma cells induced apoptosis of human hepatocytes. TUNEL staining of liver metastases revealed apoptosis of murine hepatocytes in contact with metastatic human uveal melanoma cells. Conclusion: FasL-induced apoptosis of hepatocytes in contact with FasL-positive human uveal melanoma cells may contribute to hepatic failure during metastatic disease.