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Konrad Koch, Deniz Hos, Birgit Regenfuss, Felix Bock, Jacobus Bosch, Claus Cursiefen, Ludwig Heindl; Autocrine impact of VEGF ligands in uveal melanoma cells. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4241.
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Members of the VEGF growth factor family have been shown to promote melanoma-associated angiogenesis crucial for tumor growth as well as for hematogenous and lymphatic metastatic spread. Additional to vascular processes, autocrine effects (migration, survival, proliferation) of VEGF molecules on several malignoma cells (e.g., ovarian carcinoma, pancreatic carcinoma, dermal melanoma) have been described. The purpose of this study was to investigate in vitro (I) whether uveal melanoma cells express different VEGF molecules, and (II) whether melanoma cell proliferation is influenced by VEGF or the anti-VEGF-antibody bevacizumab.
Human primary uveal melanoma cell lines (OCM-1, OCM-3, MEL-270) were cultured, RNA was isolated (RNeasy Mikro Kit, Quiagen), and cDNA was synthesized (SuperScript 3, Invitrogen). The cDNA was used to measure VEGF-A/-B/-C mRNA expression by quantitative real time RT-PCR. For the proliferation assays, melanoma cells seeded on a 96-well-plate (2000 cells/well) were incubated for 24 hours in medium containing VEGF-A (100ng/ml), or bevacizumab (250μg/ml). BrdU was added for 6 hours. Colorimetric analysis was performed after fixation and staining.
All melanoma cell lines expressed VEGF-A, -C and -D, with VEGF-A showing the most prominent expression. Melanoma cells incubated with VEGF-A showed increased proliferation in comparison with VEGF-free-medium (p<0.05). Incubation with bevacizumab resulted in decreased tumor cell proliferation compared with VEGF- and bevacizumab-free medium (p<0.05).
VEGF ligands, expressed by ocular melanoma cells may serve as autocrine growth factors beyond their well-known proangiogenic attributes. Accordingly, potential adjuvant therapeutic strategies with anti-VEGF-drugs such as bevacizumab seem to be particularly useful by addressing malignant melanoma progression in a twofold approach.
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