Premium
Down‐regulation of E‐cadherin expression in madin darby canine kidney (MDCK) cells inside tumors of nude mice
Author(s) -
Mareel Marc M.,
Behrens Jürgen,
Birchmeier Walter,
De Bruyne Georges K.,
Vleminckx Kris,
Hoogewijs Annemarie,
Fiers Walter C.,
Van Roy Frans M.
Publication year - 1991
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910470623
Subject(s) - cadherin , biology , in vitro , cell culture , cell adhesion molecule , cell–cell interaction , in vivo , nude mouse , metastasis , cancer research , cell , microbiology and biotechnology , pathology , cancer , medicine , genetics
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.