E-cadherin expression: a counterbalance for cancer cell invasion.
Invasion, eventually leading to metastasis, is presented as the result of a balance between the activation of 2 sets of genes, coined i+ (invasion promotor) and i- (invasion suppressor) genes. Experiments in vitro have indicated that the homotypic homophilic epithelial cell--cell adhesion molecule E-cadherin (L-CAM; uvomorulin; cell CAM 120/80; Arc-1; rrl antigen) is an i- gene product. In several cell families, manipulation of E-cadherin at the level of the protein by antibody-mediated inactivation, at the level of the mRNA by antisense DNA transfection, and at the level of the genome by sense DNA transfection respectively resulted in induction and suppression of invasiveness. Nude mouse tumors from non-invasive homogeneously E-cadherin-positive cell populations were found to be invasive and metastatic. These tumors expressed E-cadherin in a heterogeneous manner, the undifferentiated cells being negative; but tumor-derived cells in culture were again E-cadherin-positive, indicating downregulation of this protein by host factors. Several types of human cancers showed a similar heterogeneity suggesting a relationship between downregulation of E-cadherin and invasion. Our current research focus is on the factors responsible for E-cadherin downregulation in experimental and human cancers.
Mareel
M
M
Department of Radiotherapy and Nuclear Medicine, University of Ghent, Belgium.
Vleminckx
K
K
Vermeulen
S
S
Bracke
M
M
Van Roy
F
F
D000818:Animals; D015820:Cadherins / Q000235:genetics* / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000235:genetics*; D009374:Neoplasms, Experimental / Q000235:genetics; D010641:Phenotype
D015820:Cadherins