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@ARTICLE{Mogler:124436,
author = {C. Mogler$^*$ and C. König$^*$ and M. Wieland$^*$ and A.
Runge$^*$ and E. Besemfelder$^*$ and D. Komljenovic$^*$ and
T. Longerich and P. Schirmacher and H. G. Augustin},
title = {{H}epatic stellate cells limit hepatocellular carcinoma
progression through the orphan receptor endosialin.},
journal = {EMBO molecular medicine},
volume = {9},
number = {6},
issn = {1757-4684},
address = {Weinheim},
publisher = {Wiley-VCH},
reportid = {DKFZ-2017-01313},
pages = {741 - 749},
year = {2017},
note = {DKFZ-ZMBH Alliance},
abstract = {Hepatocellular carcinoma (HCC) is among the most common and
deadliest cancers worldwide. A major contributor to HCC
progression is the cross talk between tumor cells and the
surrounding stroma including activated hepatic stellate
cells (HSC). Activation of HSC during liver damage leads to
upregulation of the orphan receptor endosialin (CD248),
which contributes to regulating the balance of liver
regeneration and fibrosis. Based on the established role of
endosialin in regulating HSC/hepatocyte cross talk, we
hypothesized that HSC-expressed endosialin might similarly
affect cell proliferation during hepatocarcinogenesis.
Indeed, the histological analysis of human HCC samples
revealed an inverse correlation between tumor cell
proliferation and stromal endosialin expression.
Correspondingly, global genetic inactivation of endosialin
resulted in accelerated tumor growth in an inducible mouse
HCC model. A candidate-based screen of tumor lysates and
differential protein arrays of cultured HSC identified
several established hepatotropic cytokines, including IGF2,
RBP4, DKK1, and CCL5 as being negatively regulated by
endosialin. Taken together, the experiments identify
endosialin-expressing HSC as a negative regulator of HCC
progression.},
cin = {A190 / L101 / E020},
ddc = {610},
cid = {I:(DE-He78)A190-20160331 / I:(DE-He78)L101-20160331 /
I:(DE-He78)E020-20160331},
pnm = {311 - Signalling pathways, cell and tumor biology
(POF3-311)},
pid = {G:(DE-HGF)POF3-311},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:28373218},
pmc = {pmc:PMC5452049},
doi = {10.15252/emmm.201607222},
url = {https://inrepo02.dkfz.de/record/124436},
}