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Charlotta All-Ericsson, Leonard Girnita, Stefan Seregard, Armando Bartolazzi, Martine J. Jager, Olle Larsson; Insulin-like Growth Factor-1 Receptor in Uveal Melanoma: A Predictor for Metastatic Disease and a Potential Therapeutic Target. Invest. Ophthalmol. Vis. Sci. 2002;43(1):1-8.
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purpose. To investigate the expression of the insulin-like growth factor-1
receptor (IGF-1R) with special focus on its role in cell growth in
methods. Paraffin material from 36 clinicopathologically well characterized
cases of primary uveal melanomas (18 of which had metastasized to the
liver) with more than 15 years’ follow-up was used for
immunohistochemical analysis. In the experimental studies, three uveal
melanoma cell lines (OCM-1, OCM-3, and 92-1) were used. The expression
level of IGF-1R in the cell lines was modulated by glycosylation
inhibitors, and the IGF-1R was neutralized with the antibody αIR-3.
Expression of IGF-1R was assayed by Western blot analysis and
immunohistochemistry. Cell growth and survival were analyzed by cell
counting, thymidine incorporation, and viability assays.
results. Western blot analysis and immunohistochemistry confirmed that IGF-1R is
expressed in uveal melanoma. Although 10 of 18 patients who died of
metastasizing disease showed high IGF-1R expression, only 5 of 18
tumors from patients who survived for 15 years or more after
enucleation exhibited a high IGF-1R expression. Kaplan-Meier analysis
showed a significant association (P = 0.035)
between a high IGF-1R expression and death due to metastatic uveal
melanoma. Using in vitro experimental models, we found that inhibition
of the IGF-1R activity (tyrosine phosphorylation) was associated with a
drastic decrease in uveal melanoma cell viability.
conclusions. These data suggest an important role of IGF-1R in uveal melanoma. The
significant association between high IGF-1R expression and death due to
metastatic disease may be explained by the fact that IGF-1 is mainly
produced in the liver, which is the preferential site for uveal
melanoma metastases. These data also point to the possibility of
therapeutically interfering with IGF-1R, which appears to be expressed
preferentially in uveal melanomas that appear to follow an aggressive
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