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Extracellular vesicle secretion of miR‐142‐3p from lung adenocarcinoma cells induces tumor promoting changes in the stroma through cell‐cell communication
Author(s) -
Lawson James,
Dickman Christopher,
Towle Rebecca,
Jabalee James,
Javer Ariana,
Garnis Cathie
Publication year - 2019
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.22935
Subject(s) - biology , microvesicles , microbiology and biotechnology , stroma , angiogenesis , fibroblast , tumor microenvironment , cancer cell , cell signaling , cell , cancer research , microrna , signal transduction , cell culture , cancer , immunology , tumor cells , biochemistry , genetics , gene , immunohistochemistry
Extracellular vesicles (EVs) are mediators of communication between cancer cells and the surrounding tumor microenvironment. EV content is able to influence key tumorigenic changes including invasion, metastasis, and inducing pro‐tumor changes in the stroma. MiR‐142‐3p is a known tumor suppressor in LAC and was recently shown to be enriched within LAC EVs, indicating its potential as a key signaling miRNA. Our research demonstrates the role EV associated miR‐142‐3p plays when transferred from LAC cells to both endothelial and fibroblast cells. We demonstrate that transfer of miR‐142‐3p in LAC EVs to endothelial cells promotes angiogenesis through inhibition of TGFβR1. Additionally, we show EV associated miR‐142‐3p promotes the cancer‐associated fibroblast phenotype in lung fibroblast cells which we show is independent of TGFβ signaling. These findings suggest that miR‐142‐3p within LAC EVs can be transferred from LAC cells to both endothelial and fibroblast cells to promote tumor associated changes.