ADAM17 Promotes Motility, Invasion, and Sprouting of Lymphatic Endothelial Cells.

摘要: Tumor-associated lymphatic vessels actively participate in tumor progression and dissemination. ADAM17, a sheddase for numerous growth factors, cytokines, receptors, cell adhesion molecules, is believed to promote development, facilitating both proliferation migration, as well angiogenesis. In this work we addressed the issue of whether ADAM17 may also lymphangiogenesis. First, found that important migratory potential immortalized human dermal endothelial cells (LEC). When was stably silenced LEC, their not affected, but: (i) single-cell motility, (ii) migration through 3D Matrigel/collagen type I matrix, (iii) ability form sprouts matrix were significantly diminished. The differences motility between ADAM17-proficient ADAM17-silenced eliminated by inhibitors EGFR HER2, indicating ADAM17-mediated shedding factors accounts LEC potential. Interestingly, depletion affected integrin surface expression/functionality LEC. adhered plastic, collagen, fibronectin faster than counterparts. difference abolished cyclic RGD peptide, emphasizing involvement integrins process. Using soluble receptor array, identified BIG-H3 among several candidate proteins involved phenotypic behavioral changes upon silencing. additional assays, confirmed increased expression BIG-H3, TGFβ2 antilymphangiogenic effects silencing suggest further relevance target cancer therapy.