Loss of E-cadherin in multidrug resistant breast cancer cell line MCF-7/Adr: possible implication in the enhanced invasive ability.

BACKGROUND

Recently, many observations have drawn researchers' attention to study drug resistance and invasion/metastasis as a single entity. However, little evidence is available about the relationship between the multiple drug resistance (MDR) and invasion so far.

AIM: To study the relationship between the multiple drug resistance and invasive-metastatic phenotypes in cancer cells.

MATERIALS AND

METHODS

In this study, we compared the biological alterations of drug-resistant cells with their parental control and demonstrated that the drug-resistant cells have acquired enhanced invasive ability in addition to their acquired MDR phenotype.

RESULTS

Motility and invasiveness assays revealed that MCF-7 / Adr had an invasive phenotype. Light and electron microscopy showed loss of cell-cell clustering after trypsinization, loss of tight junctions and desmosomes, ultrastructural changes to the actin network and nucleus, loss of epithelial characters, and increase in filopodia in the drug resistant cell line. A major component of cell-cell junctions, E-cadherin, was shown to be expressed on the protein and RNA levels in MCF-7 but not MDF-7 / Adr cells. More protrusions (pseudopodia) on the cell surface were found in MCF-7 / Adr cells, which enable the cells to migrate and invade / metastasize. Examination of ultrastructural morphology revealed that great changes occurred in drug resistant cancer cells including absence of tight junctions/desmosomes, and dislocation of cytoskeleton microfilaments. Since the cadherin / catenin complexes are further associated with the major cytoskeleton components at cell-cell junctions, we measured E-cadherin expression in drug-resistant cells. Both Western blot and immunocytochemical staining demonstrated the loss of E-cadherin expression in MCF-7 / Adr cells. Further, RNA in situ hybridization results confirmed that loss of E-cadherin expression occurred at the transcriptional level.

CONCLUSIONS

The drug-resistant MCF-7/Adr cells were found to be more invasive/metastatic than their parental control, possibly related to the loss of E-cadherin expression.