However, we observed downregulation of ADAM-9 mRNA expression upon culture of melanoma cells within 3-dimensional lattices composed of fibrillar type I collagen, whereas culture within gels consisting of the polysaccharide alginate did not alter transcript levels.
Using RNAi this EGFR activation was further shown to depend on the metalloproteases ADAM9 and ADAM17 in SCC-9 cells. cDNA array hybridization and RT-PCR analysis showed overexpression of a Disintegrin and a Metalloproteases (ADAMs) and EGF family proligands in melanoma cell lines.
Looking for the effectors of these antineoplastic functions, we identified ADAM9 and MMP7, two metalloproteases playing a pivotal role in melanoma progression, as direct targets of miR-126&126*.
RNA analysis of melanoma cell lines with different invasive abilities showed ADAM-9 expression in varying amounts in all cell lines, independent of their invasive and metastatic capacities.
To address this question in vivo in a spontaneous melanoma model, we deleted ADAM-9 in mice carrying the hepatocyte growth factor (Hgf) transgene and knock-in mutation Cdk4<sup>R24C/R24C</sup>, demonstrated to spontaneously develop melanoma.