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Open Access 01-12-2015 | Research

CD90+ liver cancer cells modulate endothelial cell phenotype through the release of exosomes containing H19 lncRNA

Authors: Alice Conigliaro, Viviana Costa, Alessia Lo Dico, Laura Saieva, Simona Buccheri, Francesco Dieli, Mauro Manno, Samuele Raccosta, Carmine Mancone, Marco Tripodi, Giacomo De Leo, Riccardo Alessandro

Published in: Molecular Cancer | Issue 1/2015

Abstract

Background

CD90+ liver cancer cells have been described as cancer stem-cell-like (CSC), displaying aggressive and metastatic phenotype. Using two different in vitro models, already described as CD90+ liver cancer stem cells, our aim was to study their interaction with endothelial cells mediated by the release of exosomes.

Methods

Exosomes were isolated and characterized from both liver CD90+ cells and hepatoma cell lines. Endothelial cells were treated with exosomes, as well as transfected with a plasmid containing the full length sequence of the long non-coding RNA (lncRNA) H19. Molecular and functional analyses were done to characterize the endothelial phenotype after treatments.

Results

Exosomes released by CD90+ cancer cells, but not by parental hepatoma cells, modulated endothelial cells, promoting angiogenic phenotype and cell-to-cell adhesion. LncRNA profiling revealed that CD90+ cells were enriched in lncRNA H19, and released this through exosomes. Experiments of gain and loss of function of H19 showed that this LncRNA plays an important role in the exosome-mediated phenotype of endothelial cells.

Conclusions

Our data indicate a new exosome-mediated mechanism by which CSC-like CD90+ cells could influence their tumor microenvironment by promoting angiogenesis. Moreover, we suggest the lncRNA H19 as a putative therapeutic target in hepatocellular carcinoma.

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Title: CD90+ liver cancer cells modulate endothelial cell phenotype through the release of exosomes containing H19 lncRNA
Authors: Alice Conigliaro
Viviana Costa
Alessia Lo Dico
Laura Saieva
Simona Buccheri
Francesco Dieli
Mauro Manno
Samuele Raccosta
Carmine Mancone
Marco Tripodi
Giacomo De Leo
Riccardo Alessandro
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: Molecular Cancer / Issue 1/2015
Electronic ISSN: 1476-4598
DOI: https://doi.org/10.1186/s12943-015-0426-x

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