CONFLUENCE DEPENDENT RESISTANCE (CDR) TO DOXORUBICIN AND E-CADHERIN EXPRESSION IN MURINE MAMMARY CELLS

Confluence dependent resistance (CDR) is one of the principal mechanisms by which solid tumor cells resist anthracyclines. CDR is thought to be mediated by cell-cell contact which increases the fraction of non-proliferating resistant cells in a post confluence monolayer culture. As E-cadherin is a major Ca2+ dependent adhesion molecule, involved in cell-cell adhesion, differentiation and polarity of normal and cancerous epithelial cells, we decided to investigate its involvement in the CDR mechanism. In order to do this, we measured the intracellular accumulation and the cytotoxicity of doxorubicin (DXR) in four subclones, derived from the same parental murine mammary cell line (NMuMG), differing in their expression of E-cadherin. A significant reduction in DXR accumulation and cytotoxicity was observed in NM-f-ras-TD-CAMx, which expresses E-cadherin, suggesting that E-cadherin could play a role in the increase of drug resistance observed in confluent cancer cells.