Dissecting tumor cell invasion: epithelial cells acquire invasive properties after the loss of uvomorulin-mediated cell-cell adhesion.

TLDR

Invasive behavior is a critical step in tumor progression, and changes in intercellular adhesion may also drive carcinoma invasion in vivo. Inhibition of uvomorulin in MDCK cells induces invasion of collagen gels and embryonic heart tissue, and transformed MDCK cells lacking surface uvomorulin are constitutively invasive, indicating that loss of uvomorulin-mediated adhesion promotes malignant invasion.

Abstract

The generation of invasiveness in transformed cells represents an essential step of tumor progression. We show here, first, that nontransformed Madin-Darby canine kidney (MDCK) epithelial cells acquire invasive properties when intercellular adhesion is specifically inhibited by the addition of antibodies against the cell adhesion molecule uvomorulin; the separated cells then invade collagen gels and embryonal heart tissue. Second, MDCK cells transformed with Harvey and Moloney sarcoma viruses are constitutively invasive, and they were found not to express uvomorulin at their cell surface. These data suggest that the loss of adhesive function of uvomorulin (which is identical to E-cadherin and homologous to L-CAM) is a critical step in the promotion of epithelial cells to a more malignant, i.e., invasive, phenotype. Similar modulation of intercellular adhesion might also occur during invasion of carcinoma cells in vivo.