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E. S. Trocme, M. A. Economou, B. Sehat, Y. Lin, O. Larsson, S. Seregard; Nuclear IGF-1R in Uveal Melanoma, A Potential Metastatic Mediator. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5764.
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© ARVO (1962-2015); The Authors (2016-present)
Uveal melanoma is the most common primary intraocular tumour in adults with a very poor prognosis mainly due to liver metastasis. We have previously demonstrated the therapeutic potential of interfering with IGF 1R mediated signaling in uveal melanoma and other studies have linked nuclear tyrosine kinases with metastatic potential. In this study we focus on the tyrosine kinase insulin-like growth factor 1 receptor (IGF-1R) and investigate its ability to undergo nuclear translocalization in uveal melanoma.
Three commonly used uveal melanoma cell lines were used in the investigation (OCM-3, OCM-8 and 92-1). These were fractionated using a cell compartment kit followed by Western blot assays performed with Cell Signaling anti IGF-1R antibodies. Subsequent immunoflourescence studies were performed on the cell lines using the same primary antibodies used for the Western blot assays. Additionally, fresh tissue was obtained from two patients with previously untreated uveal melanoma, fixation with 4% PFA was immediate and immunoflourescence confocal laser microscopy was performed. All immunoflourescence studies were performed with secondary antibody only negative controls.
Western blot and immunoflourescence investigations consistently expressed intranuclear IGF-1R in all three cell lines. Fresh samples were both positive for intranuclear IGF-1R.
This study provides strong evidence that uveal melanoma expresses significant amounts of intranuclear IGF-1R, while further studies are required in order to elicit the prognostic value of this expression.
Confocal image of a fresh Uveal Melanoma sample with immunoflourescence targeting IGF-1R.Red=IGF-1R, Blue=Topro3 nuclear dye
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