TY  - JOUR
AU  - Wiedmann, Lena
AU  - De Angelis Rigotti, Francesca
AU  - Vaquero-Siguero, Nuria
AU  - Donato, Elisa
AU  - Espinet, Elisa
AU  - Moll, Iris
AU  - Alsina-Sanchis, Elisenda
AU  - Bohnenberger, Hanibal
AU  - Fernandez-Florido, Elena
AU  - Mülfarth, Ronja
AU  - Vacca, Margherita
AU  - Gerwing, Jennifer
AU  - Conradi, Lena-Christin
AU  - Ströbel, Philipp
AU  - Trumpp, Andreas
AU  - Mogler, Carolin
AU  - Fischer, Andreas
AU  - Rodriguez-Vita, Juan
TI  - HAPLN1 potentiates peritoneal metastasis in pancreatic cancer.
JO  - Nature Communications
VL  - 14
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Nature Publishing Group UK
M1  - DKFZ-2023-00816
SP  - 2353
PY  - 2023
N1  - #EA:A270#LA:A270#
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:37095087
DO  - DOI:10.1038/s41467-023-38064-w
UR  - https://inrepo02.dkfz.de/record/275610
ER  -