Down-regulation of E-cadherin expression in Madin Darby canine kidney (MDCK) cells inside tumors of nude mice.
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.
Mareel
M M
MM
Department of Radiotherapy and Nuclear Medicine, University Hospital, Ghent, Belgium.
Behrens
J
J
Birchmeier
W
W
De Bruyne
G K
GK
Vleminckx
K
K
Hoogewijs
A
A
Fiers
W C
WC
Van Roy
F M
FM
D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D004285:Dogs; D011905:Genes, ras; D006251:Harvey murine sarcoma virus / Q000235:genetics*; D007668:Kidney; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000473:pathology; D014183:Transplantation, Heterologous
D015820:Cadherins