The has shown that exosomes can participate

first evidence of the presence of miRNAs in exosomes was described by Valadi et
al in 2007 whom reported that exosomes contain miRNAs which can transferred
into acceptor cells and play their functional roles. Increasing evidence has
shown that exosomes can participate not only in different beneficial events,
but also in diverse pathological processes such as cancer. Cancer cells like
healthy cells secrete exosomes that carry different pathogenic cargos but due
to the regulatory roles of miRNAs in gene expression they have attracted a lot
of attention to themselves. Tumor-derived
exosomal miRNAs can lead to induce malignant transformation in healthy cells, angiogenesis,
cell proliferation, metastasis, drug resistance and immune modulation. For example, exosomal miR-21 released by
transformed lung cancer cells leads to
increased VEGF production and promotion of angiogenesis
through a STAT3 dependent mechanism in nearby
normal bronchial cells. Interestingly, it has been shown that hypoxia can promote the tumor
angiogenesis by inducing the secretion of the angiogenic factors by the
exosomes in tumor cells. Under hypoxic conditions, A549 lung cancer cells
released exosomal miR-494 to their surrounding endothelial cells which promoted
the angiogenesis by activation of Akt/eNOS pathway and suppression of PTEN.

Cancer metastasis is a complex process that lead to
the formation of secondary tumors at a distant site. This event occurs through
a series of steps: (i) local tumor cell invasion, (ii)
intravasation, (iii) survival in the circulatory system, (iv) extravasation and
(v) colonization of distant organ sites. Recently,
many articles have reported that tumor released exosomal miRNAs can participate
in tumor
cell migration and metastasis. For example, exosomal miR-105 derived from MCF-10A
and MDA-MB-231cells (breast cancer cell lines) stimulated metastasis to the
lung and brain through downregulating the tight junction protein ZO-1 in endothelial
cells. Interestingly, it has been reported that tumor derived exosomal miR-21
and miR-29a lead to tumor growth and metastasis by binding to
toll-like receptors (TRL) on immune cells causing the activation of the TLR-mediated
NF-?B (nuclear factor kappa-light-chain enhancer of activated B cells). Moreover,
miR-21 containing exosomes have been indicated that significantly enhanced the
migration and invasion of recipient esophageal cancer cells by targeting programmed cell death 4 (PDCD4) and
activating its downstream c-Jun N-terminal kinase (JNK) signaling pathway. Exosomal
miRNAs can also be effective on the drug response. Recently, Qin and coworkers
reported that exosomes derived from cisplatin resistance lung cancer cells, which were characterized by prominent low
expression of miR-100–5p, are capable of inducing drug resistance in recipient
cells through exosomal
miR-100–5p-dependent manner. Furthermore, blockage of miR-9 through the delivery
of anti-miR-9 by mesenchymal stem cells derived exosomes reversed the
expression of the multidrug transporter and sensitized the glioblastoma
multiforme (GBM) cells to treatments

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