ADAM10 correlates with uveal melanoma metastasis and promotes in vitro invasion

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1138-1148
Number of pages11
JournalPigment Cell and Melanoma Research
Volume27
Issue number6
DOIs
Publication statusPublished - Nov 1 2014

Keywords

  • ADAM10
  • ADAM17
  • C-Met
  • Gene expression
  • Invasion
  • Uveal melanoma

ASJC Scopus subject areas

  • Dermatology
  • Oncology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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