TY  - JOUR
AU  - Mogler, Carolin
AU  - König, Courtney
AU  - Wieland, Matthias
AU  - Runge, Anja
AU  - Besemfelder, Eva
AU  - Komljenovic, Dorde
AU  - Longerich, Thomas
AU  - Schirmacher, Peter
AU  - Augustin, Hellmut G
TI  - Hepatic stellate cells limit hepatocellular carcinoma progression through the orphan receptor endosialin.
JO  - EMBO molecular medicine
VL  - 9
IS  - 6
SN  - 1757-4684
CY  - Weinheim
PB  - Wiley-VCH
M1  - DKFZ-2017-01313
SP  - 741 - 749
PY  - 2017
N1  - DKFZ-ZMBH Alliance
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:28373218
C2  - pmc:PMC5452049
DO  - DOI:10.15252/emmm.201607222
UR  - https://inrepo02.dkfz.de/record/124436
ER  -