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 uveal melanoma. 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 alphaIR-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 clinical course.
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 uveal melanoma. 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 alphaIR-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 clinical course.
Authors: Jason J Luke; Pierre L Triozzi; Kyle C McKenna; Erwin G Van Meir; Jeffrey E Gershenwald; Boris C Bastian; J Silvio Gutkind; Anne M Bowcock; Howard Z Streicher; Poulam M Patel; Takami Sato; Jeffery A Sossman; Mario Sznol; Jack Welch; Magdalena Thurin; Sara Selig; Keith T Flaherty; Richard D Carvajal Journal: Pigment Cell Melanoma Res Date: 2014-09-01 Impact factor: 4.693
Authors: Nathalie A Kolandjian; Caimiao Wei; Sapna P Patel; Jessica L Richard; Tina Dett; Nicholas E Papadopoulos; Agop Y Bedikian Journal: Am J Clin Oncol Date: 2013-10 Impact factor: 2.339
Authors: Chuan He Yang; Junming Yue; Susan R Pfeffer; Meiyun Fan; Elena Paulus; Amira Hosni-Ahmed; Michelle Sims; Sohail Qayyum; Andrew M Davidoff; Charles R Handorf; Lawrence M Pfeffer Journal: J Biol Chem Date: 2014-07-24 Impact factor: 5.157
Authors: Robert Folberg; Shrihari S Kadkol; Shahar Frenkel; Klara Valyi-Nagy; Martine J Jager; Jacob Pe'er; Andrew J Maniotis Journal: Invest Ophthalmol Vis Sci Date: 2008-08-08 Impact factor: 4.799