The Insulin–Like Growth Factor–1 Receptor (IGF–1R) Inhibitor PPP Reduces the Incidence of Uveal Melanoma Micrometastases in the Liver

Abstract

Purpose: : In uveal melanoma metastasis is the crucial event determining survival of the patients. We have previously reported data indicating that the cyclolignan PPP, which is an inhibitor of the IGF–1R phosphorylation, efficiently blocks growth and viability of uveal melanoma cells in cultures and in xenografted mice. In this study we aimed to investigate the effects of PPP on the uveal melanoma metastasis in the liver.

Methods: : Ten–week–old pathogen–free SCID mice were used. OCM–1 cells were injected s.c. Experimental treatments with PPP were performed. Liver tissues from control and PPP treated mice were prepared for histology.

Results: : We found that early, short treatments with PPP drastically delayed tumor formation and we could also demonstrate that the incidence of micrometastases in the liver of uveal melanoma xenografted mice was drastically reduced

Conclusions: : Our study provides further support for an important role of IGF–1R in uveal melanoma and raises the possibility of using IGF–1R inhibitors in the treatment of ongoing disease as well as in prevention of development of metastases.

Keywords: tumors • melanoma