ADAM8 expression in invasive breast cancer promotes tumor dissemination and metastasis. Issue 2 (27th December 2013)

• Record Type: Journal Article
• Authors: Romagnoli, Mathilde; Mineva, Nora D; Polmear, Michael; Conrad, Catharina; Srinivasan, Srimathi; Loussouarn, Delphine; Barillé‐Nion, Sophie; Georgakoudi, Irene; Dagg, Áine; McDermott, Enda W; Duffy, Michael J; McGowan, Patricia M.; Schlomann, Uwe; Parsons, Maddy; Bartsch, Jörg W; Sonenshein, Gail E
• Is Part Of: EMBO molecular medicine. Volume 6:Issue 2(2014:Feb.)
• Page Start: 278
• Page End: 294
• Publication Date: 2013-12-27
• Subjects: Molecular biology -- Periodicals; Medical genetics -- Periodicals; Pathology, Molecular -- Periodicals; 616.04205
• DOI: 10.1002/emmm.201303373
• Languages: English
• ISSNs: 1757-4676

Abstract

<abstract abstract-type="synopsis" xml:lang="en" id="emmm201303373-abs-0002"> <title>Synopsis</title> <p> <boxed-text content-type="graphic" id="emmm201303373-blkfxd-0001" position="anchor" orientation="portrait"> <graphic position="anchor" mimetype="image" xlink:href="ark:/27927/pgg4snhnzfh" orientation="portrait" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /> </boxed-text> </p> <p>The transmembrane protein ADAM8 is shown to be a crucial player in multiple steps of breast tumorigenesis, notably in angiogenesis and cancer cell adhesion to the endothelium. The results validate ADAM8 as novel target for the treatment of aggressive triple‐negative breast cancer</p> <p> <list id="emmm201303373-list-0001" list-type="bullet"> <list-item> <p>The transmembrane ADAM8 protein is expressed in primary human breast tumors compared to normal breast tissue, and especially in triple‐negative breast cancers (TNBC), which currently have no targeted therapies.</p> </list-item> <list-item> <p>High levels of ADAM8 expression predict poor breast cancer clinical outcome and are detected in half of patient metastases.</p> </list-item> <list-item> <p>ADAM8 promotes tumor growth and dissemination in an orthotopic mouse model by stimulating angiogenesis (via the release of VEGF‐A and other pro‐angiogenic growth factors) and tumor cell intra/extravasation (via activation of β1‐integrin).</p> </list-item> <list-item> <p>Treatment of mice with a monoclonal antibody targeting ADAM8 extracellular domains initiated at the time of TNBC cell implantation in the mammary fat pad significantly reduces tumor growth, angiogenesis and metastasis.</p> </list-item> <list-item> <p>Treatment of pre‐existing tumors with the ADAM8 antibody in a neoadjuvant setting profoundly reduces metastases in a mouse resection model, further validating ADAM8 as a therapeutic target of TNBC.</p> </list-item> </list> </p> </abstract>