title: ADAM10 correlates with uveal melanoma metastasis and promotes in vitro invasion.
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.
authors.affiliation: IRCCS A.O.U. San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
authors.forename: Rosaria
authors.initials: R
authors.lastname: Gangemi
authors.forename: Adriana
authors.initials: A
authors.lastname: Amaro
authors.forename: Alice
authors.initials: A
authors.lastname: Gino
authors.forename: Gaia
authors.initials: G
authors.lastname: Barisione
authors.forename: Marina
authors.initials: M
authors.lastname: Fabbi
authors.forename: Ulrich
authors.initials: U
authors.lastname: Pfeffer
authors.forename: Antonella
authors.initials: A
authors.lastname: Brizzolara
authors.forename: Paola
authors.initials: P
authors.lastname: Queirolo
authors.forename: Sandra
authors.initials: S
authors.lastname: Salvi
authors.forename: Simona
authors.initials: S
authors.lastname: Boccardo
authors.forename: Marina
authors.initials: M
authors.lastname: Gualco
authors.forename: Francesco
authors.initials: F
authors.lastname: Spagnolo
authors.forename: Martine J
authors.initials: MJ
authors.lastname: Jager
authors.forename: Carlo
authors.initials: C
authors.lastname: Mosci
authors.forename: Armando
authors.initials: A
authors.lastname: Rossello
authors.forename: Silvano
authors.initials: S
authors.lastname: Ferrini
mesh_terms: D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism*; D000072197:ADAM10 Protein; D000072198:ADAM17 Protein; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D019859:Proto-Oncogene Proteins c-met / Q000097:blood / Q000235:genetics / Q000378:metabolism; D012307:Risk Factors; D012995:Solubility; D014604:Uveal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D000098943:Uveal Melanoma
chemical_list: D008565:Membrane Proteins; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human; C000606463:Adam17 protein, mouse
keywords: ADAM10; ADAM17; c-Met; gene expression; invasion; uveal melanoma