P-glycoprotein is overexpressed in human and canine inflammatory breast cancer cell lines but not in xenotransplanted mouse tumours.

Introduction: Multidrug resistance (MDR) to anti-cancer drugs is a major issue for the treatment of breast cancer. Overexpression of the transmembrane protein P-glycoprotein (PGP) is involved in the MDR mechanism. PGP acts as an ATP-dependent drug transporter and pumps a wide spectrum of drugs out of the cell. Inflammatory breast cancer is a special type of breast cancer with the worst prognosis and a high mortality due to the lack of effective treatments. Therefore, many investigations are conducted to find effective therapies. The aim of the present study was to determine the immunolabelling of PGP in human and canine inflammatory mammary cancer cell lines and in the corresponding xenograft tumours in mice. Materials and Methods: Immunohistochemistry against PGP was performed in human and canine inflammatory mammary cancer cell lines (SUM-149 and IPC-366, respectively) growing in adherent and non-adherent (mammospheres) conditions and in the corresponding mouse xenografts. Results: Adherent cells of both cell lines showed the characteristic membranous expression of PGP, with!5% having cytoplasmic immunolabelling. A cytoplasmic and membranous clumped immunolabelling was found in the mammospheres of the cell lines. In contrast, tumours of the corresponding xenotransplanted mice did not express PGP in most of the cells:!5%of cells expressed a slight clumped membranous labelling. Conclusions: The lack of PGP immunolabelling found in the mouse xenografts suggests a loss of MDR related to PGP expression in the murine model. Although further studies are necessary, caution should be considered in experimental therapeutic studies carried out in xenografted mice.