title: 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 mechanisms contribute to MDR, such as P-glycoprotein (Pgp/ABCB1) activity that promotes 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 microparticles (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 microRNA transfer and NFκB and Yb-1 activation. Therefore, our results indicate that MP can induce a multifactorial phenotype in sensitive cancer cells.
authors.affiliation: Program of Hemato-Oncology Molecular, Brazilian National Cancer Institute, Rio de Janeiro, Brazil.
authors.forename: Paloma Silva
authors.initials: PS
authors.lastname: de Souza
authors.forename: André L S
authors.initials: AL
authors.lastname: Cruz
authors.forename: João P B
authors.initials: JP
authors.lastname: Viola
authors.forename: Raquel C
authors.initials: RC
authors.lastname: Maia
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D063646:Carcinogenesis / Q000378:metabolism; D055252:Cell-Derived Microparticles / Q000502:physiology*; D018920:Coculture Techniques; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D020014:K562 Cells; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D035683:MicroRNAs; D016328:NF-kappa B; D051057:Proto-Oncogene Proteins c-akt
keywords: Inhibitors of apoptosis proteins; NFκB; P-glycoprotein; microparticles; multidrug resistance