Angiostatin produced by certain primary uveal melanoma cell lines impedes the development of liver metastases

Objectives: To evaluate the ability of human uveal melanomas to produce ang iostatin in vitro and the effect of angiostatin on the development of liver metastases in vivo. Methods: Human uveal melanoma cell lines (OCM1, OCM3, MEL202, MEL285, 92-1, OM431, and OMM1) were assayed for their ability to produce angiostatin in vitro by an angiostatin bioassay and by Western blot analysis. The OCM3 and OMM1 tumor cells were inoculated either in the posterior or the anterior s egment of nude mice. One group of mice in each experiment underwent enuclea tion and hepatic metastases were assayed by histopathologic and liver funct ion analysis. Results: OCM1, OCM3, and 92-1 cell lines significantly inhibited bovine end othelial cell proliferation in vitro and generated 38-Kd angiostatin molecu les. Enucleation of eyes containing OCM3 in the posterior segment resulted in a higher number of metastatic foci (26.5) in that group compared with th e nonenucleated group of mice (11.17). After enucleation, elevated levels o f serum aspartate transaminase and alanine aminotransferase were observed i n mice bearing OCM3 in either anterior or posterior segments. The enucleati on of eyes containing OMM1 (nonangiostatin-producing cells) had no signific ant effect on liver metastasis. Conclusion: By removing a source of angiostatin, enucleation of melanoma-co ntaining eyes may unwittingly exacerbate the metastatic potential of uveal melanomas. Clinical Relevance: In certain circumstances, enucleating a melanoma-contai ning eye may unwittingly exacerbate metastatic disease. The results also su ggest that exogenous angiostatin may have potential therapeutic implication s in the management of patients with primary intraocular melanomas.