Paloma Silva de Souza1, Roberta Soares Faccion1, Paula Sabbo Bernardo2, Raquel Ciuvalschi Maia3. 1. Laboratório de Hemato-Oncologia Celular e Molecular, Programa de Hemato-Oncologia Molecular, Brazilian National Cancer Institute (INCA), Rio de Janeiro, Brazil. 2. Programa de Pós-Graduação em Oncologia, INCA, Rio de Janeiro, Brazil. 3. Laboratório de Hemato-Oncologia Celular e Molecular, Programa de Hemato-Oncologia Molecular, Brazilian National Cancer Institute (INCA), Rio de Janeiro, Brazil. rcmaia@inca.gov.br.
Abstract
BACKGROUND: Microparticles (MPs) or ectosomes are small enclosed fragments (from 0.2 to 2 μm in diameter) released from the cellular plasma membrane. Several oncogenic molecules have been identified inside MPs, including soluble proteins XIAP, survivin, metalloproteinases, CX3CL1, PYK2 and other microRNA-related proteins; membrane proteins EGFR, HER-2, integrins and efflux pumps; and messenger RNAs and microRNAs miR-21, miR-27a, let-7, miR-451, among others. Studies have shown that MPs transfer their cargo to neoplastic or non-malignant cells and thus contribute to activation of oncogenic pathways, resulting in cell survival, drug resistance and cancer dissemination. DISCUSSION AND CONCLUSION: This review summarizes recent findings on MP biogenesis and the role of the MPs cargo in cancer and discusses some of the RNAs and proteins involved. In addition, the discussion covers evidence of (1) how and which signaling pathways can be activated by MPs in recipient cells; (2) recipient cell-type selectivity in incorporation of proteins and RNAs transported by MPs; and (3) how upon stimulation, stromal cells release MPs, promoting resistance to chemotherapeutics and invasiveness in cancer cells.
BACKGROUND: Microparticles (MPs) or ectosomes are small enclosed fragments (from 0.2 to 2 μm in diameter) released from the cellular plasma membrane. Several oncogenic molecules have been identified inside MPs, including soluble proteins XIAP, survivin, metalloproteinases, CX3CL1, PYK2 and other microRNA-related proteins; membrane proteins EGFR, HER-2, integrins and efflux pumps; and messenger RNAs and microRNAs miR-21, miR-27a, let-7, miR-451, among others. Studies have shown that MPs transfer their cargo to neoplastic or non-malignant cells and thus contribute to activation of oncogenic pathways, resulting in cell survival, drug resistance and cancer dissemination. DISCUSSION AND CONCLUSION: This review summarizes recent findings on MP biogenesis and the role of the MPs cargo in cancer and discusses some of the RNAs and proteins involved. In addition, the discussion covers evidence of (1) how and which signaling pathways can be activated by MPs in recipient cells; (2) recipient cell-type selectivity in incorporation of proteins and RNAs transported by MPs; and (3) how upon stimulation, stromal cells release MPs, promoting resistance to chemotherapeutics and invasiveness in cancer cells.
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