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Effects of Insulin-like Growth Factor Receptor Inhibition on Human Melanomas in Culture and in Athymic Mice¹

Strong Children's Research Center, Departments of Pediatrics [R. W. F., S. E. H.] and Pathology and Laboratory Animal Medicine [R. B. B.], University of Rochester School of Medicine and Dentistry, Rochester, New York 14642

The role of the insulin-like growth factor (IGF) receptor in regulating the growth of melanoma cells was evaluated by examining the effect of antibody-mediated IGF receptor inhibition on the growth of four human melanoma cell lines in culture and as xenotransplants in athymic mice. All four cell lines expressed typical type I IGF receptors and an antibody to this receptor (IR-3) inhibited [¹²⁵I]IGF-I binding. However, the cell lines varied widely in their in vitro responsiveness to IGF-I and IR-3: in the WM 373 and WM 852 cell lines, IGF-I stimulated cell replication and IR-3 inhibited this response, whereas in the WM 239-A and WM 266-4 cell lines neither the growth factor nor the antibody affected growth. A wide variation was also observed in the effect of the antibody on the growth of the different cell lines as xenotransplants but this qualitatively correlated with the responses observed in vitro: IR-3 treatment significantly inhibited the growth of the WM 373 and WM 852 xenotransplants but did not inhibit the growth of the WM 239-A or WM 266-4 xenotransplants and may even have had a slight stimulatory effect. These results indicate that the IGF receptor pathway is a functional regulator of the in vivo growth of some melanomas and that this is reflected in the activity of this pathway as determined in vitro. These findings suggest that therapies aimed at inhibiting the IGF pathway may be beneficial in treating some melanomas.

¹ Supported by NIH Grant R01-CA38981.

² To whom requests for reprints should be addressed, at Division of Endocrinology, Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Box 777, 601 Elmwood Avenue, Rochester, NY 14642.

Received 11/17/92. Accepted 3/29/93.

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