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C.A. Ericsson, A. Girnita, M. Economou, M. Axelson, S. Seregard, O. Larsson, L. Girnita; The Insulin–like Growth Factor–1 Receptor (IGF–1R) Inhibitor PPP Attenuates Crucial Metastasis Mechanisms of Uveal Melanoma: Implications for a New Treatment Regimen . Invest. Ophthalmol. Vis. Sci. 2005;46(13):4618.
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Purpose: We previously demonstrated that the cyclolignan PPP efficiently blocks the insulin–like growth facotor–1 receptor (IGF–1R) in uveal melanoma cell lines. In this study the purpose was to investigate the effect of PPP in vivo and to determine if PPP is affecting the factors contributing to tumor dissemination. Methods: The uveal melanoma cell line OCM–1 was injected subcutaneously into SCID mice and experimental treatment with PPP was performed. Adhesion of uveal melanoma cells to ECM proteins was assessed using a CytoMatrixTM kit, the gelatinolytic activity of MMP–2 was analyzed by zymography and to assay the effect of PPP on migration and invasion of uveal melanoma cells we used BD BioCoatTM MatrigelTM chambers. Results: PPP efficiently blocks growth and viability of uveal melanoma cells in cultures and in xenografted mice. In particular, treatment with PPP attenuated several crucial metastatic mechanisms, including tumor cell adhesion to major extracellular matrix proteins, activity of matrix metalloproteinase 2, cell migration as well as invasion through basement membranes and endothelial cell layers. Conclusions: Our data provide evidence that IGF–1R is crucial for the metastatic phenotype of uveal melanoma cells and suggest that IGF–1R inhibitors may be used as an adjuvant therapy to prevent development of metastases.
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