Microvesicles mediate transfer of P-glycoprotein to paclitaxel-sensitive A2780 human ovarian cancer cells, conferring paclitaxel-resistance

Abstract

The overexpression of P-glycoprotein (P-gp) causes resistance to chemotherapy in human ovarian cancer. However, the underlying mechanism remains unclear. In the present study, we showed that, at membrane-bound protein level, P-gp was ‘shared’ between human ovarian cancer cells by the intercellular transfer of microvesicles (MVs). Paclitaxel-resistant human ovarian cancer cells (A2780/PTX) readily formed and released P-gp-containing MVs into the extracellular space compared with the wild-type parental line (A2780/WT). Shedding MVs bound to the chemosensitive A2780/WT cells in a time- and dose-dependent manner, transferring P-gp via the microenvironment. MV-mediated transfer of P-gp led to redistribution of the chemotherapeutic drug adriamycin in recipient cells (A2780/WT), which displayed 5- and 5-fold higher resistance to adriamycin and paclitaxel, respectively. Thus, these findings demonstrate a new mechanism of drug-resistance acquisition via MVs.