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Bradley Gao, Levon Djenderedjian, William Coppess, Zachary Goldsmith, Matthew W Wilson, Vanessa Marie Morales; Pharmacological Inhibition of Paxillin Reduces Cell Proliferation in Uveal Melanoma Cell Lines. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4118. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Uveal Melanoma (UM) is the most common primary intraocular tumor in adults. Predominantly, it presents in the choroid, but may also be present in the iris and ciliary body. Here, we investigate the contributions of the cytoskeletal adaptor paxillin in UM cell cycle regulation by using the paxillin inhibitor 6-B345TTQ.
We cultured the primary UM cell lines Mel270 and 92.1 in the presence or absence of 20ng/mL of Hepatocyte Growth Factor (HGF), which is highly abundant in the liver microenvironment and exposed them to increasing concentrations of the paxillin inhibitor 6-B345TTQ. We investigated the percentage of cells expressing the cyclins associated with G1 and S phase, namely Cyclin D1, E and A, and the inhibitors p21 and p27.
Our work shows a significant reduction in the percentage of UM expressing Cyclin E, required to transition from G1 to S, when treated by paxillin inhibitor or by paxillin inhibitor and HGF in primary UM cells [untreated: 4.87%±0.24; paxillin: 3.06%±0.4; paxillin + HGF: 3.7%±0.47; p=0.0006]. We also examined p21, shown to be high in invasive UM, and found Mel270 showed a reduction in p21 levels in HGF + paxillin inhibitor (p=0.08) cultures. UM cell line 92.1 also showed a significant reduction in p21 (p=0.05).
More experiments are underway to delineate the potential role of inhibition of paxillin to control UM cell proliferation. Our results suggest inhibition of paxillin could be used as an adjunct therapy in UM.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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