Plasmin produces an E-cadherin fragment that stimulates cancer cell invasion.
Matrix metalloproteases from the cell surface cleave an 80 kDa E-cadherin fragment (sE-CAD) that induces invasion of cancer cells into collagen type I and inhibits cellular aggregation. Conditioned media from MDCKts.srcCl2 cells at 40 degrees C and 35 degrees C, PCm.src5 and COLO-16 cells at 37 degrees C contained spontaneously released sE-CAD; these 48 h old conditioned media were capable of inhibiting E-cadherin functions in a paracrine way. Here we show direct cleavage of the extracellular domain of E-cadherin by the serine protease plasmin. sE-CAD released by plasmin inhibits E-cadherin functions as evidenced by induction of invasion into collagen type I and inhibition of cellular aggregation. This functional inhibition by sE-CAD was reversed by aprotinin or by immunoadsorption on protein Sepharose 4 fast flow beads with antibodies against the extracellular part of E-cadherin. Our results demonstrate that plasmin produces extracellular E-cadherin fragments which regulate E-cadherin function in cells containing an intact E-cadherin/catenin complex.
Ryniers
Filip
F
Laboratory of Experimental Cancerology, Department of Radiotherapy and Nuclear Medicine, University Hospital Ghent, Belgium.
Stove
Christophe
C
Goethals
Marc
M
Brackenier
Liesbeth
L
Noë
Veerle
V
Bracke
Marc
M
Vandekerckhove
Joël
J
Mareel
Marc
M
Bruyneel
Erik
E
D000818:Animals; D015820:Cadherins / Q000187:drug effects / Q000378:metabolism*; D002460:Cell Line; D024042:Collagen Type I; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004285:Dogs; D005341:Fibrinolysin / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000473:pathology*; D019899:Paracrine Communication; D010446:Peptide Fragments / Q000502:physiology*; D012995:Solubility
D015820:Cadherins; D024042:Collagen Type I; D017077:Culture Media, Conditioned; D010446:Peptide Fragments; D005341:Fibrinolysin