Expression of insulin‐like growth factor‐1 receptor in metastatic uveal melanoma and implications for potential autocrine and paracrine tumor cell growth |
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Authors: | Peter A. McCue Tiziana DeAngelis Renato Baserga Ami Fujii Hallgeir Rui Michael J. Mastrangelo Takami Sato |
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Affiliation: | 1. Department of Pathology, Anatomy & Cell Biology, Thomas Jefferson University, , Philadelphia, PA, USA;2. Department of Cancer Biology, Thomas Jefferson University, , Philadelphia, PA, USA;3. Department of Medical Oncology, Thomas Jefferson University, , Philadelphia, PA, USA |
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Abstract: | We investigated the importance of the insulin‐like growth factor‐1 receptor (IGF‐1R) in hepatic metastases of uveal melanoma. The expression pattern of IGF‐1R in archival tissue samples of hepatic metastasis from 24 patients was analyzed by immunohistochemistry. All the samples of hepatic metastases stained positive for IGF‐1R. To investigate the biological role of IGF‐1R on the growth of metastatic uveal melanoma, a long‐term cell line obtained from a hepatic metastasis (TJU‐UM001) was evaluated. TJU‐UM001 expressed cell surface IGF‐1R (>90%) and proliferated in response to exogenous and endogenous insulin‐like growth factor‐1 (IGF‐1). Correlatively, anti‐IGF‐1R antibody completely blocked IGF‐1‐induced growth of TJU‐UM001 cells. IGF‐1 preferentially induced phosphorylation of Akt (S473) in quiescent TJU‐UM001 cells, and this was blocked by anti‐IGF‐1R antibody. This study suggests that autocrine and paracrine mechanisms underlie IGF‐1‐induced growth of metastatic uveal melanoma and underscore the potential benefit of IGF‐1 or IGF‐1R antagonism in treatment for metastatic uveal melanoma. |
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Keywords: | uveal melanoma hepatic metastasis insulin‐like growth factor‐1 insulin‐like growth factor‐1 receptor paracrine autocrine |
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