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  • ADAM10 correlates with uveal melanoma metastasis and promotes in vitro invasion.

ADAM10 correlates with uveal melanoma metastasis and promotes in vitro invasion.

Pigment cell & melanoma research (2014-08-16)
Rosaria Gangemi, Adriana Amaro, Alice Gino, Gaia Barisione, Marina Fabbi, Ulrich Pfeffer, Antonella Brizzolara, Paola Queirolo, Sandra Salvi, Simona Boccardo, Marina Gualco, Francesco Spagnolo, Martine J Jager, Carlo Mosci, Armando Rossello, Silvano Ferrini
ABSTRACT

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 ADAM10, MET, and, to a lesser extent, ADAM17 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, ADAM10 silencing inhibits UM cell invasion driven by FCS or HGF, while ADAM17 silencing has a limited effect. Altogether our data indicate that ADAM10 has a pro-invasive role and may contribute to UM progression.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
HGF mouse, recombinant, expressed in Hi-5 Insect cells, ≥95% (SDS-PAGE), ≥95% (HPLC)
Sigma-Aldrich
Hepatocyte Growth Factor human, HGF, recombinant, expressed in Baculovirus infected High-5 cells, suitable for cell culture
Sigma-Aldrich
Hepatocyte Growth Factor human, HGF, recombinant, expressed in NSO cells, suitable for cell culture
Sigma-Aldrich
HGF human, recombinant, expressed in CHO cells, ≥97% (SDS-PAGE), ≥97% (HPLC)