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Role of Exosomic MicroRNAs in Cancer Cell Cross‐Talk within the Tumor Microenvironment
Author(s) -
Fabbri Muller,
Wise Petra,
Murtadha Mariam,
Neviani Paolo,
Challagundla Kishore
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.221.2
Subject(s) - microvesicles , microrna , tumor microenvironment , cancer research , cancer cell , cancer , secretion , tumor necrosis factor alpha , biology , function (biology) , mechanism (biology) , microbiology and biotechnology , immunology , gene , tumor cells , endocrinology , genetics , philosophy , epistemology
MicroRNAs (miRNAs) regulate gene expression in cells and are frequently dys‐regulated in human cancers. Recent evidence indicates that miRNAs are released by normal and cancer cells within microvesicles called exosomes and can be functionally transferred to surrounding cells. We showed that cancer cell secreted exosomic miRNAs can function as agonists of Toll‐like receptor 8 (TLR8) in tumor‐associated macrophages (TAMs), favoring a pro‐tumoral and pro‐metastatic tumor microenvironment. These effects are mediated by the activation of the NF‐kB pathway and increased secretion of interleukin‐6 and tumor necrosis factor alpha by TAMs. We also report that the cross‐talk elicited by exosomic miRNAs is responsible for increased drug resistance in neuroblastoma cells, through exchange of exosomic miRNAs by cancer‐cell “educated” TAMs. This newly identified mechanism harbors promising potentials to prevent and/or overcome the development of resistance to drugs by cancer cells, which still represents the most prominent cause of cancer‐related deaths.