Expression of insulin-like growth factor-1 receptor in metastatic uveal melanoma and implications for potential autocrine and paracrine tumor cell growth

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.

Keywords: autocrine; hepatic metastasis; insulin-like growth factor-1; insulin-like growth factor-1 receptor; paracrine; uveal melanoma.