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http://hdl.handle.net/2445/200926
Title: | HAPLN1 potentiates peritoneal metastasis in pancreatic cancer |
Author: | Wiedmann, Lena Angelis Rigotti, Francesca de Vaquero Siguero, Nuria Donato, Elisa Espinet, Elisa Moll, Iris Alsina Sanchís, Elisenda Bohnenberger, Hanibal Fernández Florido, Elena Mülfarth, Ronja Vacca, Margherita Gerwing, Jennifer Conradi, Lena-Christin Ströbel, Philipp Trumpp, Andreas Mogler, Carolin Fischer, Andreas Rodríguez Vita, Juan |
Keywords: | Càncer de pàncrees Metàstasi Pancreas cancer Metastasis |
Issue Date: | 24-Apr-2023 |
Publisher: | Springer Science and Business Media LLC |
Abstract: | The presence of peritoneal metastasis in pancreatic cancers is associated with poor prognosis. Here the authors show that hyaluronan and proteoglycan link protein-1 (HAPLN1) promotes tumour cell plasticity and pro-tumoral immune microenvironment to facilitate peritoneal dissemination in pancreatic cancers. 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. |
Note: | Reproducció del document publicat a: https://doi.org/10.1038/s41467-023-38064-w |
It is part of: | Nature Communications, 2023, vol. 14, num. 1 |
URI: | http://hdl.handle.net/2445/200926 |
Related resource: | https://doi.org/10.1038/s41467-023-38064-w |
ISSN: | 2041-1723 |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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