| http://purl.uniprot.org/citations/28553955 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/28553955 | http://www.w3.org/2000/01/rdf-schema#comment | "ADAM-9 is a metalloproteinase expressed in peritumoral areas by invading melanoma cells and by adjacent peritumoral stromal cells; however, its function in stromal and melanoma cells is not fully understood. 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 Cdk4R24C/R24C, demonstrated to spontaneously develop melanoma. Spontaneous melanoma arose less frequently in ADAM-9-deleted mice than in controls. Similarly reduced tumor numbers (although with faster growth kinetics) were detected upon induction of melanoma with 7,12-dimethylbenz[a]anthracene (DMBA). However, more lesions were induced at early time points in the absence of ADAM-9. Increased initial and decreased late tumor numbers were paralleled by altered tumor cell proliferation, but not apoptosis or inflammation. Importantly, significantly reduced lung metastases were detected upon ADAM-9 deletion. Using in vitro assays to address this effect mechanistically, we detected reduced adhesion and transmigration of ADAM-9-silenced melanoma cells to/through the endothelium. This implies that ADAM-9 functionally and cell autonomously mediates extravasation of melanoma cells. In vitro and in vivo we demonstrated that the basement membrane (BM) component laminin β3-chain is a direct substrate of ADAM-9, thus contributing to destabilization and disruption of the BM barrier during invasion. In in vitro invasion assays using human melanoma cells and skin equivalents, depletion of ADAM-9 resulted in decreased invasion of the BM, which remained almost completely intact, as shown by continuous staining for laminin β3-chain. Importantly, supplying soluble ADAM-9 to the system reversed this effect. Taken together, our data show that melanoma derived ADAM-9 autonomously contributes to melanoma progression by modulating cell adhesion to the endothelium and altering BM integrity by proteolytically processing the laminin-β3 chain. This newly described process and ADAM-9 itself may represent potential targets for anti-tumor therapies."xsd:string |
| http://purl.uniprot.org/citations/28553955 | http://purl.org/dc/terms/identifier | "doi:10.1038/onc.2017.162"xsd:string |
| http://purl.uniprot.org/citations/28553955 | http://purl.uniprot.org/core/author | "Mauch C."xsd:string |
| http://purl.uniprot.org/citations/28553955 | http://purl.uniprot.org/core/author | "Zigrino P."xsd:string |
| http://purl.uniprot.org/citations/28553955 | http://purl.uniprot.org/core/author | "Giebeler N."xsd:string |
| http://purl.uniprot.org/citations/28553955 | http://purl.uniprot.org/core/author | "Tuting T."xsd:string |
| http://purl.uniprot.org/citations/28553955 | http://purl.uniprot.org/core/author | "Landsberg J."xsd:string |
| http://purl.uniprot.org/citations/28553955 | http://purl.uniprot.org/core/author | "Schonefuss A."xsd:string |
| http://purl.uniprot.org/citations/28553955 | http://purl.uniprot.org/core/date | "2017"xsd:gYear |
| http://purl.uniprot.org/citations/28553955 | http://purl.uniprot.org/core/name | "Oncogene"xsd:string |
| http://purl.uniprot.org/citations/28553955 | http://purl.uniprot.org/core/pages | "5058-5067"xsd:string |
| http://purl.uniprot.org/citations/28553955 | http://purl.uniprot.org/core/title | "Deletion of ADAM-9 in HGF/CDK4 mice impairs melanoma development and metastasis."xsd:string |
| http://purl.uniprot.org/citations/28553955 | http://purl.uniprot.org/core/volume | "36"xsd:string |
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