Expression of insulin-like growth factor-1 receptor in metastatic uveal melanoma and implications for potential autocrine and paracrine tumor cell growth. Pigment Cell Melanoma Res 2014 Mar;27(2):297-308
Date
12/21/2013Pubmed ID
24354797DOI
10.1111/pcmr.12206Scopus ID
2-s2.0-84894085123 (requires institutional sign-in at Scopus site) 42 CitationsAbstract
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.
Author List
Yoshida M, Selvan S, McCue PA, DeAngelis T, Baserga R, Fujii A, Rui H, Mastrangelo MJ, Sato TMESH terms used to index this publication - Major topics in bold
AdultAged
Aged, 80 and over
Antibodies
Autocrine Communication
Cell Line, Tumor
Cell Proliferation
Female
Humans
Insulin-Like Growth Factor I
Male
Melanoma
Middle Aged
Neoplasm Metastasis
Paracrine Communication
Receptor, IGF Type 1
Signal Transduction
Uveal Neoplasms
