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@ARTICLE{Wiedmann:275610,
author = {L. Wiedmann$^*$ and F. De Angelis Rigotti$^*$ and N.
Vaquero-Siguero$^*$ and E. Donato$^*$ and E. Espinet$^*$ and
I. Moll$^*$ and E. Alsina-Sanchis$^*$ and H. Bohnenberger
and E. Fernandez-Florido$^*$ and R. Mülfarth$^*$ and M.
Vacca$^*$ and J. Gerwing$^*$ and L.-C. Conradi and P.
Ströbel and A. Trumpp$^*$ and C. Mogler and A. Fischer$^*$
and J. Rodriguez-Vita$^*$},
title = {{HAPLN}1 potentiates peritoneal metastasis in pancreatic
cancer.},
journal = {Nature Communications},
volume = {14},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Nature Publishing Group UK},
reportid = {DKFZ-2023-00816},
pages = {2353},
year = {2023},
note = {#EA:A270#LA:A270#},
abstract = {Pancreatic ductal adenocarcinoma (PDAC) frequently
metastasizes into the peritoneum, which contributes to poor
prognosis. Metastatic spreading is promoted by cancer cell
plasticity, yet its regulation by the microenvironment is
incompletely understood. Here, we show that the presence of
hyaluronan and proteoglycan link protein-1 (HAPLN1) in the
extracellular matrix enhances tumor cell plasticity and PDAC
metastasis. Bioinformatic analysis showed that HAPLN1
expression is enriched in the basal PDAC subtype and
associated with worse overall patient survival. In a mouse
model for peritoneal carcinomatosis, HAPLN1-induced
immunomodulation favors a more permissive microenvironment,
which accelerates the peritoneal spread of tumor cells.
Mechanistically, HAPLN1, via upregulation of tumor necrosis
factor receptor 2 (TNFR2), promotes TNF-mediated
upregulation of Hyaluronan (HA) production, facilitating
EMT, stemness, invasion and immunomodulation. Extracellular
HAPLN1 modifies cancer cells and fibroblasts, rendering them
more immunomodulatory. As such, we identify HAPLN1 as a
prognostic marker and as a driver for peritoneal metastasis
in PDAC.},
cin = {A270 / A010},
ddc = {500},
cid = {I:(DE-He78)A270-20160331 / I:(DE-He78)A010-20160331},
pnm = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
pid = {G:(DE-HGF)POF4-311},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37095087},
doi = {10.1038/s41467-023-38064-w},
url = {https://inrepo02.dkfz.de/record/275610},
}