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M. Kouch-El Filali, P. A. van der Velden, L. V. Ly, G. P. M. Luyten, M. J. Jager; Uveal Melanoma: Hypoxia Influences VEGF-A Production but Not Proliferation. Invest. Ophthalmol. Vis. Sci. 2008;49(13):66. doi: https://doi.org/.
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It is assumed that tumors over 1.5 mm in size will need to develop their own blood supply in order to obtain enough oxygen to sustain their growth. It may be that local ischemia induces the production of VEGF-A in the tumor, which is necessary for blood vessel formation. Previous studies showed the presence of VEGF-A in the fluids of eyes with a uveal melanoma, where both the retinal tissue as well as the tumor tissue could be the source of VEGF-A (1). As ischemia is a trigger of VEGF-A production, we wondered whether ischemia would induce uveal melanoma cells to produce VEGF-A in vitro.
Nine uveal melanoma cell lines and one primary tumor cell culture were cultured under either normoxic (20% O2) or hypoxic (1% O2) conditions. Cell proliferation was measured by mitochondrial function using the WST-1 assay. VEGF-A production was measured by ELISA and intracellular expression of VEGF-A was determined by real time RT-PCR.
We found an induction of VEGF-A expression (RT-PCR) and production (ELISA) in all uveal melanoma cell lines under hypoxic conditions (>2 fold), while three cell lines showed an increase as high as 9-10 fold. The primary tumor cell culture showed an even higher expression of VEGF-A (11 fold). Cell proliferation was inhibited under hypoxic conditions in all cell lines.
Hypoxia induced uveal melanoma cells to express and produce VEGF-A, but did not stimulate cell growth. This phenomenon may contribute to the induction of blood vessel growth in uveal melanomas in vivo.1) Missotten GS et al. Vascular endothelial growth factor a in eyes with uveal melanoma. Arch Ophthalmol 2006; 124(10):1428-1434.
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