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FGF2 promotes metastasis of uveal melanoma cells via store-operated calcium entry

Authors Wang Y, Bao X, Zhang Z, Sun Y, Zhou X

Received 10 March 2017

Accepted for publication 1 October 2017

Published 8 November 2017 Volume 2017:10 Pages 5317—5328

DOI https://doi.org/10.2147/OTT.S136677

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Lucy Goodman

Peer reviewer comments 2

Editor who approved publication: Dr Faris Farassati

Yanyan Wang,1 Xiuli Bao,2 Zhiyong Zhang,3 Yi Sun,4 Xiyuan Zhou1

1Department of Ophthalmology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 2Department of Ophthalmology, 3Department of Nuclear Medicine, 4Department of Ophthalmology, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia, People’s Republic of China

Abstract:
Uveal melanoma (UM), the most common primary intraocular malignancy in adults, is highly metastatic and associated with dismal prognosis. Fibroblast growth factor 2 (FGF2) has been shown to induce cell proliferation and angiogenesis of melanoma and other malignancies. However, the expression of FGF2 in UM and its effects on melanoma cell migration are not well known. In this study, we found FGF2 expression was related to UM histological subtype and presence of metastasis. In vitro experiments showed that FGF2 treatment caused increased horizontal and vertical migration and F-actin cytoskeleton assembly as well as decreased adhesive activity of MUM2B cells, together with increased intracellular calcium concentration and expression of ORAI1 and STIM1 – two key regulatory proteins of store-operated calcium entry (SOCE). The mouse xenograft model showed that MUM2B cells with FGF2 stimulation grew into larger tumor masses and were prone to metastasis. In addition, the SOCE inhibitor 2-aminoethoxydiphenyl borate (2-APB) reversed all of these effects of FGF2. Finally, human UM samples and mouse xenograft model samples were used to confirm the correlation of FGF2 with ORAI1 and STIM1 expression. Taken together, our study suggests that FGF2 promotes metastasis of UM via SOCE.

Keywords: FGF2, uveal melanoma, metastasis, store-operated calcium entry, ORAI1, STIM1
 

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