title: Release of an invasion promoter E-cadherin fragment by matrilysin and stromelysin-1.
abstract: The function of many transmembrane molecules can be altered by cleavage and subsequent release of their ectodomains. We have investigated ectodomain cleavage of the cell-cell adhesion and signal-transducing molecule E-cadherin. The E-cadherin ectodomain is constitutively shed from the surface of MCF-7 and MDCKts.srcC12 cells in culture. Release of the 80 kDa soluble E-cadherin fragment is stimulated by phorbol-12-myristate-13-acetate and is inhibited by overexpression of the tissue inhibitor of metalloproteinases-2. The metalloproteinases matrilysin and stromelysin-1 both cleave E-cadherin at the cell surface and release sE-CAD into the medium. The soluble E-cadherin fragment thus released inhibits E-cadherin functions in a paracrine way, as indicated by induction of invasion into collagen type I and inhibition of E-cadherin-dependent cell aggregation. Our results, therefore, suggest a novel mechanism by which metalloproteinases can influence invasion.
authors: Laboratory of Experimental Cancerology, Department of Radiotherapy and Nuclear Medicine, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium.
authors: V
authors: V
authors: Noë
authors: B
authors: B
authors: Fingleton
authors: K
authors: K
authors: Jacobs
authors: H C
authors: HC
authors: Crawford
authors: S
authors: S
authors: Vermeulen
authors: W
authors: W
authors: Steelant
authors: E
authors: E
authors: Bruyneel
authors: L M
authors: LM
authors: Matrisian
authors: M
authors: M
authors: Mareel
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D004285:Dogs; D006801:Humans; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism*; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D015820:Cadherins; D019278:Matrix Metalloproteinase 3; D020783:Matrix Metalloproteinase 7