Abstract
Abstract: :
Purpose: Recently it was discovered that some choroidal melanomas form non–endothelial–lined, PAS–positive, blood–carrying tubes via a process called vasculogenic mimicry. The ability of tumor cells to form these channels and their presence in tumors have been linked to tumor aggressiveness. Up to the present time, there are no animal models of both aggressive (PAS–loop–positive) and nonaggressive (PAS–loop–negative) choroidal melanoma. The purpose of this study was to develop new xenograft models of human choroidal melanoma that demonstrate the PAS–staining patterns associated with nonaggressive and aggressive tumors. Methods: Nude, athymic WAG/Nij–rnu rats were used in this study. Three human choroidal melanoma cell lines (OCM–1, M619, and C918) were used to grow spheroids in vitro. OCM–1 cells were supplied by Dr. June Kan–Mitchell, Wayne State University. C918 and M619 cells were provided by Drs. Mary Hendrix and Karla Daniels, University of Iowa. OCM–1 is characterized as a nonaggressive tumor, based on its inability to form PAS–positive channels in vitro. M619 and C918 form these channels and have been designated aggressive choroidal melanoma lines. Spheroids of each cell type were injected into the choroidal space transclerally. Tumors were grown for 1 to 4 weeks, and histology was performed to evaluate tumor growth. PAS staining was performed to determine the pattern of PAS labeling. OCM–1, M619, and C918 spheroids were implanted in the right eyes of 10, 10, and 3 rats, respectively. Results: Tumors from all cell lines could be grown as orthotopic xenografts in nude rats. Implantation of OCM–1 spheroids resulted in tumor growth in all 10 rats. Growth of M619 and C918 xenografts could be histologically verified in 9 of 10 rats and 3 of 3 rats, respectively. PAS staining revealed loops and networks, typical of aggressive tumors, in 100% of C918 and M619 xenografts. Only 4 of 10 OCM–1 xenografts showed PAS–positive loops. The other 6 showed either only perivascular PAS staining or parallel PAS–positive lines, indicative of nonaggressive tumors. Conclusions: It is possible to grow human choroidal melanoma orthotopic xenografts in nude rats that reproduce the expected PAS–staining patterns seen in aggressive and nonaggressive choroidal melanomas. As hypothesized, the nonaggressive OCM–1 cells were capable of generating tumors with PAS–positive patterns indicative of nonaggressive tumors, although not 100% of the time. The two aggressive cell lines, M619 and C918, always resulted in tumors that showed the looping PAS patterns associated with aggressive tumors.
Keywords: melanoma • oncology