Down‐regulation of E‐cadherin expression in madin darby canine kidney (MDCK) cells inside tumors of nude mice

Abstract

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.

HOXD3-overexpression increases integrin αvβ3 expression and deprives E-cadherin while it enhances cell motility in A549 cells

“…Dysfunction of the E-cadherin-mediated cell adhesion system plays an important role in acquisition of more malignant phenotype by tumor cells [31]. Experimental biological approaches also show that E-cadherin functions as an invasion-suppressor [20][21][22]. In the present study, the addition of function-blocking antibody to E-cadherin into the assay increased migratory activity of the integrin β3-transfectants, suggesting that Ecadherin plays a role in preventing the tumor cells from migrating from wound edge.…”

“…We earlier reported that the HOXD3-overexpression led the loss of E-cadherin expression in A549 cells [16]. In vitro experiments on cultured cells indicate Ecadherin has invasion-suppressing properties [20][21][22]. Therefore, we next examined the expression and function of E-cadherin in the integrin β3-overexpressing cells.…”

BPD-MA-mediated photosensitization in vitro and in vivo: cellular adhesion and β1 integrin expression in ovarian cancer cells

“…However, once maintained in culture for a few days, ascites cells return to an in vitro adhesion pattern (data not shown). This difference probably reflects an in vivo signal which is absent in vitro, due to a change of phenotype which has been reported (Mareel et al, 1991). Alternatively, the decreased adhesion seen in vivo may result from ligand occupation of the binding sites (Wilhelm et al, 1988) and OVCAR 3 ascites are found to contain glandular structures ex vivo which are not seen when OVCAR 3 cells are maintained in vitro similar to the situation with mouse mammary cells (Aggeler et al, 1991).…”

E-cadherin as a prognostic indicator in primary breast cancer

“…In addition, a transgenic mouse model of pancreatic β cell carcinoma revealed that loss of E-CD expression coincided with transition from well differentiated adenoma to invasive carcinoma (Perl et al, 1998). However, some studies have indicated that the loss of E-CD is reversible, for example in ras-transformed Madin Darby Canine kidney cells in nude mice, possibly due to interaction with the host environment (Mareel et al, 1991). Dysfunction of α-catenin has also been implicated.…”