Tspan8-Tumor Extracellular Vesicle-Induced Endothelial Cell and Fibroblast Remodeling Relies on the Target Cell-Selective Response.
Animals
Cell Communication
Cell Line, Tumor
Down-Regulation
/ genetics
Endothelial Cells
/ metabolism
Extracellular Vesicles
/ metabolism
Fibroblasts
/ metabolism
Lung
/ cytology
MicroRNAs
/ genetics
Models, Biological
Neovascularization, Physiologic
RNA, Long Noncoding
/ genetics
RNA, Messenger
/ genetics
Rats
Signal Transduction
Tetraspanins
/ metabolism
Transcription, Genetic
Up-Regulation
/ genetics
endothelial cells
fibroblasts
mRNA
message transfer
ncRNA
non-transformed target remodeling
tetraspanin 8
tumor exosomes
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
29 01 2020
29 01 2020
Historique:
received:
18
12
2019
revised:
17
01
2020
accepted:
26
01
2020
entrez:
5
2
2020
pubmed:
6
2
2020
medline:
11
2
2021
Statut:
epublish
Résumé
Tumor cell-derived extracellular vesicles (TEX) expressing tetraspanin Tspan8-alpha4/beta1 support angiogenesis. Tspan8-alpha6/beta4 facilitates lung premetastatic niche establishment. TEX-promoted target reprogramming is still being disputed, we explored rat endothelial cell (EC) and lung fibroblast (Fb) mRNA and miRNA profile changes after coculture with TEX. TEX were derived from non-metastatic BSp73AS (AS) or metastatic BSp73ASML (ASML) rat tumor lines transfected with Tspan8 (AS-Tspan8) or Tspan8-shRNA (ASML-Tspan8kd). mRNA was analyzed by deep sequencing and miRNA by array analysis of EC and Fb before and after coculture with TEX. EC and Fb responded more vigorously to AS-Tspan8- than AS-TEX. Though EC and Fb responses differed, both cell lines predominantly responded to membrane receptor activation with upregulation and activation of signaling molecules and transcription factors. Minor TEX-initiated changes in the miRNA profile relied, at least partly, on long noncoding RNA (lncRNA) that also affected chromosome organization and mRNA processing. These analyses uncovered three important points. TEX activate target cell autonomous programs. Responses are initiated by TEX targeting units and are target cell-specific. The strong TEX-promoted lncRNA impact reflects lncRNA shuttling and location-dependent distinct activities. These informations urge for an in depth exploration on the mode of TEX-initiated target cell-specific remodeling including, as a major factor, lncRNA.
Identifiants
pubmed: 32013145
pii: cells9020319
doi: 10.3390/cells9020319
pmc: PMC7072212
pii:
doi:
Substances chimiques
MicroRNAs
0
RNA, Long Noncoding
0
RNA, Messenger
0
Tetraspanins
0
Tspan8 protein, rat
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
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