Role of Fas ligand in uveal melanoma-induced liver damage

Background: Uveal melanoma, the most common adult intraocular malignancy, m etastasizes preferentially to the liver. Areas of cell death surrounding uv eal melanoma metastases were observed in the livers of mice. We hypothesize d that uveal melanoma cells might express Fas ligand (FasL), facilitating F asL-mediated apoptosis of Fas-expressing hepatocytes. Purpose: To determine whether Fas ligand (FasL)-expressing human uveal melanoma cells induce apo ptosis of human hepatocytes in vitro and in vivo. Methods: Human uveal mela noma cell lines were assayed for FasL expression by flow cytometry and immu nohistology. A human hepatocyte cell line was assayed for Fas expression by flow cytometry. Apoptosis of hepatocytes was detected by annexin V stainin g in vitro, and terminal deoxynucleotidyl transferase nick end labeling (TU NEL) in vivo. Results: Human uveal melanoma cell lines expressed FasL, as d etermined by flow cytometry and immunohistology. Human hepatocytes were Fas -positive by flow cytometry. In vitro, annexin V staining revealed that hum an uveal melanoma cells induced apoptosis of human hepatocytes. TUNEL stain ing of liver metastases revealed apoptosis of murine hepatocytes in contact with metastatic human uveal melanoma cells. Conclusion: FasL-induced apopt osis of hepatocytes in contact with FasL-positive human uveal melanoma cell s may contribute to hepatic failure during metastatic disease.