Genetic manipulation of E-cadherin expression by epithelial tumor cells reveals an invasion suppressor role.
A cDNA encoding the cell-cell adhesion molecule E-cadherin was transfected into highly invasive epithelial tumor cell lines of dog kidney or mouse mammary gland origin. Transfectants with a homogeneously high expression of E-cadherin showed a reproducible loss of activity in two types of in vitro invasion assays. Invasiveness of these transfectants could be reinduced specifically by treatment with anti-E-cadherin antibodies. In vivo, they formed partly differentiated tumors, instead of fully undifferentiated tumors. Alternatively, a plasmid encoding E-cadherin-specific anti-sense RNA was introduced into noninvasive ras-transformed cells with high endogenous E-cadherin expression. The resulting down-regulation, albeit partial, rendered the cells invasive. These data provide direct evidence that E-cadherin acts as an invasion suppressor molecule.
Vleminckx
K
K
Laboratory of Molecular Biology, State University of Ghent, Belgium.
Vakaet
L
L
Mareel
M
M
Fiers
W
W
van Roy
F
F
D000818:Animals; D015820:Cadherins / Q000032:analysis / Q000235:genetics*; D002454:Cell Differentiation; D002460:Cell Line; D002642:Chick Embryo; D005455:Fluorescent Antibody Technique; D011905:Genes, ras; D051379:Mice; D008819:Mice, Nude; D009206:Myocardium / Q000473:pathology; D009361:Neoplasm Invasiveness; D009374:Neoplasms, Experimental / Q000235:genetics* / Q000473:pathology; D010957:Plasmids; D014162:Transfection
D015820:Cadherins