Down-regulation of E-cadherin expression in Madin Darby canine kidney (MDCK) cells inside tumors of nude mice

Int J Cancer. 1991 Apr 1;47(6):922-8. doi: 10.1002/ijc.2910470623.


The 120-kDa cell-cell adhesion molecule E-cadherin is localized at the epithelial junctional complex and participates in the organization and maintenance of epithelia. The Madin Darby canine kidney (MDCK) cell line expresses E-cadherin in a stable way and forms polarized epitheloid structures in vitro. Harvey-murine-sarcoma-virus-transformed derivatives (MDCK-ras) produce malignant (i.e., invasive and metastatic) tumors in nude mice. We obtained evidence that E-cadherin is down-regulated in nude mouse tumors and that this down-regulation is reversible. MDCK-ras-e cell lines were cloned in vitro from MDCK-ras cell cultures. They showed an epithelioid morphotype and expressed E-cadherin at homogeneously high level. This characteristic has been conserved for at least 60 passages in vitro. MDCK-ras-e cells were not invasive in vitro. When injected into nude mice, however, they produced invasive and metastatic tumors. Primary tumors as well as large metastases were heterogeneous, showing E-cadherin-positive well differentiated epithelial structures and E-cadherin-negative undifferentiated areas. Metastasis-derived cell cultures contained both E-cadherin-positive and E-cadherin-negative MDCK-ras-e cells during early passages in vitro. During further culture, however, they regained the homogeneous E-cadherin-positive characteristic of the original MDCK-ras-e cell line. The behavior of MDCK-ras-e cells in vitro, as compared with its in vivo behavior, points to the existence of host factors which are able to down-regulate E-cadherin expression. We hypothesize that this down-regulation plays a basic role in invasion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cadherins / metabolism*
  • Cell Line
  • Cell Transformation, Neoplastic*
  • Dogs
  • Genes, ras*
  • Harvey murine sarcoma virus / genetics*
  • Kidney
  • Mice
  • Mice, Nude
  • Neoplasms, Experimental / pathology
  • Transplantation, Heterologous


  • Cadherins