Angiostatin produced by certain primary uveal melanoma cell lines impedes the development of liver metastases.
OBJECTIVE
To evaluate the ability of human uveal melanomas to produce angiostatin 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 segment of nude mice. One group of mice in each experiment underwent enucleation and hepatic metastases were assayed by histopathologic and liver function analysis.


RESULTS
OCM1, OCM3, and 92-1 cell lines significantly inhibited bovine endothelial cell proliferation in vitro and generated 38-Kd angiostatin molecules. Enucleation of eyes containing OCM3 in the posterior segment resulted in a higher number of metastatic foci (26.5) in that group compared with the nonenucleated group of mice (11.17). After enucleation, elevated levels of serum aspartate transaminase and alanine aminotransferase were observed in mice bearing OCM3 in either anterior or posterior segments. The enucleation of eyes containing OMM1 (nonangiostatin-producing cells) had no significant effect on liver metastasis.


CONCLUSIONS
By removing a source of angiostatin, enucleation of melanoma-containing eyes may unwittingly exacerbate the metastatic potential of uveal melanomas.


CONCLUSIONS
In certain circumstances, enucleating a melanoma-containing eye may unwittingly exacerbate metastatic disease. The results also suggest that exogenous angiostatin may have potential therapeutic implications in the management of patients with primary intraocular melanomas.
Apte
R S
RS
Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9057, USA.
Niederkorn
J Y
JY
Mayhew
E
E
Alizadeh
H
H
D000410:Alanine Transaminase / Q000097:blood; D043168:Angiostatins; D000818:Animals; D000970:Antineoplastic Agents; D001219:Aspartate Aminotransferases / Q000097:blood; D015153:Blotting, Western; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D018920:Coculture Techniques; D004730:Endothelium, Vascular / Q000166:cytology; D015353:Eye Enucleation; D006801:Humans; D008111:Liver Function Tests; D008113:Liver Neoplasms / Q000378:metabolism / Q000517:prevention & control* / Q000556:secondary; D008546:Melanoma, Experimental / Q000378:metabolism / Q000517:prevention & control* / Q000556:secondary; D051379:Mice; D008819:Mice, Nude; D010446:Peptide Fragments / Q000096:biosynthesis*; D010958:Plasminogen / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured / Q000378:metabolism* / Q000473:pathology; D014604:Uveal Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*
D000970:Antineoplastic Agents; D010446:Peptide Fragments; D043168:Angiostatins; D010958:Plasminogen; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase