Release of an invasion promoter E-cadherin fragment by matrilysin and stromelysin-1.
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.
Noë
V
V
Laboratory of Experimental Cancerology, Department of Radiotherapy and Nuclear Medicine, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium.
Fingleton
B
B
Jacobs
K
K
Crawford
H C
HC
Vermeulen
S
S
Steelant
W
W
Bruyneel
E
E
Matrisian
L M
LM
Mareel
M
M
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
D015820:Cadherins; D019278:Matrix Metalloproteinase 3; D020783:Matrix Metalloproteinase 7