title: 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.
authors.affiliation: Department of Medical Oncology, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Makoto
authors.initials: M
authors.lastname: Yoshida
authors.forename: Senthamil
authors.initials: S
authors.lastname: Selvan
authors.forename: Peter A
authors.initials: PA
authors.lastname: McCue
authors.forename: Tiziana
authors.initials: T
authors.lastname: DeAngelis
authors.forename: Renato
authors.initials: R
authors.lastname: Baserga
authors.forename: Ami
authors.initials: A
authors.lastname: Fujii
authors.forename: Hallgeir
authors.initials: H
authors.lastname: Rui
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Mastrangelo
authors.forename: Takami
authors.initials: T
authors.lastname: Sato
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000494:pharmacology; D019898:Autocrine Communication / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D008297:Male; D008545:Melanoma / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D019899:Paracrine Communication / Q000187:drug effects; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014604:Uveal Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D000098943:Uveal Melanoma
chemical_list: D000906:Antibodies; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1
keywords: autocrine; hepatic metastasis; insulin-like growth factor-1; insulin-like growth factor-1 receptor; paracrine; uveal melanoma