TY - JOUR
T1 - Effect of anti-ganglioside antibodies on the metastatic spread of intraocular melanomas in a nude mouse model of human uveal melanoma
AU - Niederkorn, Jerry Y.
AU - Mellon, Jessamee
AU - Pidherney, Marsha
AU - Mayhew, Elizabeth
AU - Anand, Rajiv
N1 - Funding Information:
ACKNOWLEDGMENTS This work support by an unrestricted grant from Research t o Prevent Blindness, Inc., New York and NIH grant CA30276. Dr. Niederkorn i s a Research to Prevent Blindness, Inc. Senior Scientific Investigator. We gratefully acknowledge the generosity of Dr. June Kan-Mitchell (University of Southern California School of Medicine) for providing OCM-1 and OCM-3 uveal melanoma cell lines, Dr. Ralph Reisfeld (Scripps Clinic and Research Institute) for graciously providing anti-GD2 and anti-GD3 monoclonal antibodies, and Dr. Larry Donoso (Wills Eye Hospital) for his advice and his generous g i f t o f MAb8-1H monoclonal antibody. We also thank Mr. John Horner for providing excellent photographic assistance.
PY - 1993
Y1 - 1993
N2 - In vivo and in vitro studies were performed to determine: (a) if human uveal melanoma cells expressed GD2 and GD3 gangliosides; (b) if anti-GD2 monoclonal antibodies would inhibit the propensity of human uveal melanoma cells to localize in the liver following intravenous injection; and (c) if anti-GD2 monoclonal antibody would reduce the spontaneous metastasis of primary intraocular melanomas in nude mice. The results showed that all three of the human uveal melanoma cell lines tested expressed GD2 and GD3 gangliosides in vitro and in vivo. The human uveal melanoma cell lines preferentially localized in the liver and entered the hepatic parenchyma following spontaneous metastasis from the eyes of nude mice. In vivo administration of anti-GD2 monoclonal antibody produced a sharp reduction in the number of uveal melanoma cells that disseminated to the liver following either intravenous injection or by spontaneous metastasis from primary intraocular melanomas. Collectively, the results demonstrate that uveal melanoma cells display a propensity to localize in the liver after entering the bloodstream; however, this localization can be significantly inhibited by in vivo administration of antiganglioside antibodies. The expression of GD2 and GD3 surface gangliosides on uveal melanomas and the capacity of anti-ganglioside antibodies to inhibit metastasis formation in mouse models of ocular and cutaneous melanomas raise the possibility of implementing anti-ganglioside antibodies as potential therapeutic agents for the management of uveal melanoma.
AB - In vivo and in vitro studies were performed to determine: (a) if human uveal melanoma cells expressed GD2 and GD3 gangliosides; (b) if anti-GD2 monoclonal antibodies would inhibit the propensity of human uveal melanoma cells to localize in the liver following intravenous injection; and (c) if anti-GD2 monoclonal antibody would reduce the spontaneous metastasis of primary intraocular melanomas in nude mice. The results showed that all three of the human uveal melanoma cell lines tested expressed GD2 and GD3 gangliosides in vitro and in vivo. The human uveal melanoma cell lines preferentially localized in the liver and entered the hepatic parenchyma following spontaneous metastasis from the eyes of nude mice. In vivo administration of anti-GD2 monoclonal antibody produced a sharp reduction in the number of uveal melanoma cells that disseminated to the liver following either intravenous injection or by spontaneous metastasis from primary intraocular melanomas. Collectively, the results demonstrate that uveal melanoma cells display a propensity to localize in the liver after entering the bloodstream; however, this localization can be significantly inhibited by in vivo administration of antiganglioside antibodies. The expression of GD2 and GD3 surface gangliosides on uveal melanomas and the capacity of anti-ganglioside antibodies to inhibit metastasis formation in mouse models of ocular and cutaneous melanomas raise the possibility of implementing anti-ganglioside antibodies as potential therapeutic agents for the management of uveal melanoma.
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U2 - 10.3109/02713689308999459
DO - 10.3109/02713689308999459
M3 - Article
C2 - 8319494
AN - SCOPUS:0027160382
SN - 0271-3683
VL - 12
SP - 347
EP - 358
JO - Current Eye Research
JF - Current Eye Research
IS - 4
ER -