ADAM10 correlates with uveal melanoma metastasis and promotes in vitro invasion. (11th September 2014)

• Record Type: Journal Article
• Authors: Gangemi, Rosaria; Amaro, Adriana; Gino, Alice; Barisione, Gaia; Fabbi, Marina; Pfeffer, Ulrich; Brizzolara, Antonella; Queirolo, Paola; Salvi, Sandra; Boccardo, Simona; Gualco, Marina; Spagnolo, Francesco; Jager, Martine J.; Mosci, Carlo; Rossello, Armando; Ferrini, Silvano
• Is Part Of: Pigment cell & melanoma research. Volume 27:Number 6(2014:Nov.)
• Page Start: 1138
• Page End: 1148
• Publication Date: 2014-09-11
• Subjects: Melanoma -- Periodicals; Chromatophores -- Periodicals; Animal pigments -- Periodicals; 616.99477
• DOI: 10.1111/pcmr.12306
• Languages: English
• ISSNs: 1755-1471

Abstract

<abstract abstract-type="main" id="pcmr12306-abs-0001"> <title>Summary</title> <p>Uveal melanoma (UM) is a rare ocular tumor that may lead to deadly metastases in 50% of patients. A disintegrin and metalloproteinase (ADAM)10, ADAM17, and the HGF‐receptor c‐Met support invasiveness in different tumors. Here, we report that high <italic>ADAM10, MET, </italic> and, to a lesser extent, <italic>ADAM17</italic> gene expression correlates with poor progression‐free survival in UM patients (hazard ratio 2.7, 2.6, and 1.9, respectively). About 60% of primary UM expresses c‐Met and/or ADAM10 proteins. Four UM cell lines display high levels of ADAM10 and ADAM17, which constitutively cleave c‐Met, inducing the release of soluble c‐Met. ADAM10/17 pharmacological inhibition or gene silencing reduces c‐Met shedding, but has limited impact on surface c‐Met, which is overexpressed. Importantly, <italic>ADAM10</italic> silencing inhibits UM cell invasion driven by FCS or HGF, while <italic>ADAM17</italic> silencing has a limited effect. Altogether our data indicate that ADAM10 has a pro‐invasive role and may contribute to UM progression.</p> </abstract>