Microparticles induce multifactorial resistance through oncogenic pathways independently of cancer cell type

Abstract

Multidrug resistance (MDR) is considered a multifactorial event that favors cancer cells becoming resistant to several chemotherapeutic agents. Numerous mecha nisms contribute to MDR, such as P-glycoprotein (Pgp ⁄ ABCB1) activity that pro motes drug efflux, overexpression of inhibitors of apoptosis proteins (IAP) that contribute to evasion of apoptosis, and oncogenic pathway activation that favors cancer cell survival. MDR molecules have been identified in membrane microparti cles (MP) and can be transferred to sensitive cancer cells. By co-culturing MP derived from MDR-positive cells with recipient cells, we showed that sensitive cells accumulated Pgp, IAP proteins and mRNA. In addition, MP promoted microR NA transfer and NFjB and Yb-1 activation. Therefore, our results indicate that MP can induce a multifactorial phenotype in sensitive cancer cells.