Imperial College London
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DrJoseCortes Lopez

Faculty of Engineering, Department of Bioengineering

 
 
 
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Contact

 

+44 (0)7944 338 144j.e.corteslopez Website

 
 
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Location

 

B-122Bessemer BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Sarper:2016:10.1038/srep27639,
author = {Sarper, M and Cortes, E and Lieberthal, T and del, Rio Hernandez A},
doi = {10.1038/srep27639},
journal = {Scientific Reports},
title = {ATRA modulates mechanical activation of TGF-β by pancreatic stellate cells},
url = {http://dx.doi.org/10.1038/srep27639},
volume = {6},
year = {2016}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The hallmark of pancreatic ductal adenocarcinoma (PDAC) is abundant desmoplasia, which is orchestrated by pancreatic stellate cells (PSCs) and accounts for the majority of the stroma surrounding the tumour. Healthy PSCs are quiescent, but upon activation during disease progression, they adopt a myofibroblast-contractile phenotype and secrete and concomitantly reorganise the stiff extracellular matrix (ECM). Transforming growth factor β (TGF-β) is a potent activator of PSCs, and its activation requires spatiotemporal organisation of cellular and extracellular cues to liberate it from an inactive complex with latent TGF-β binding protein (LTBP). Here we study the mechanical activation of TGF-β by PSCs in vitro by investigating LTBP-1 organisation with fibrillar fibronectin and show that all trans-retinoic acid (ATRA), which induces PSC quiescence, down-regulates the ability of PSCs to mechanically organise LTBP-1 and activate TGF-β through a mechanism involving myosin II dependent contractility. Therefore, ATRA inhibits the ability of PSCs to mechanically release active TGF-β, which might otherwise act in an autocrine manner to sustain PSCs in an active state and a tumour-favouring stiff microenvironment.
AU  - Sarper,M
AU  - Cortes,E
AU  - Lieberthal,T
AU  - del,Rio Hernandez A
DO  - 10.1038/srep27639
PY  - 2016///
SN  - 2045-2322
TI  - ATRA modulates mechanical activation of TGF-β by pancreatic stellate cells
T2  - Scientific Reports
UR  - http://dx.doi.org/10.1038/srep27639
UR  - http://hdl.handle.net/10044/1/33218
VL  - 6
ER  -
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