HAPLN1 potentiates peritoneal metastasis in pancreatic cancer.

Fecha de publicación: 24/04/2023

Autores de CIPF

Francesca De Angelis Rigotti

Autor
Juan Rodriguez Vita

Autor

Participantes ajenos a CIPF

Wiedmann L
Vaquero-Siguero N
Donato E
Espinet E
Moll I
Alsina-Sanchis E
Bohnenberger H
Fernandez-Florido E
Mülfarth R
Vacca M
Gerwing J
Conradi LC
Ströbel P
Trumpp A
Mogler C
Fischer A

Grupos de Investigación

Laboratorio Comunicación Tumor-Estroma

Jefe/a de Grupo Junior

Juan Rodriguez Vita

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.

Datos de la publicación

ISSN/ISSNe:: 2041-1723, 2041-1723
Tipo:: Article
Páginas:: 2353-2353
DOI:: 10.1038/s41467-023-38064-w
PubMed:: 37095087

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Métricas

Filiaciones

Wiedmann L:: Division Vascular Signaling and Cancer, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany

Faculty of Biosciences, University of Heidelberg, 69120, Heidelberg, Germany
De Angelis Rigotti F:: Division Vascular Signaling and Cancer, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany

Tumor-Stroma Communication Laboratory, Centro de Investigación Príncipe Felipe, 46012, Valencia, Spain
Vaquero-Siguero N:: Division Vascular Signaling and Cancer, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany
Donato E:: Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany

HI-STEM - Heidelberg Institute for Stem Cell Technology and Experimental Medicine gGmbH, 69120, Heidelberg, Germany
Espinet E:: Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany

HI-STEM - Heidelberg Institute for Stem Cell Technology and Experimental Medicine gGmbH, 69120, Heidelberg, Germany

Department of Pathology and Experimental Therapy, School of Medicine, University of Barcelona (UB), L'Hospitalet de Llobregat, Barcelona, Spain

Molecular Mechanisms and Experimental Therapy in Oncology Program (Oncobell), Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, 08908, Spain
Moll I:: Division Vascular Signaling and Cancer, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany
Alsina-Sanchis E:: Division Vascular Signaling and Cancer, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany

Institute for Clinical Chemistry, University Medical Center Göttingen, 37075, Göttingen, Germany
Bohnenberger H:: Institute of Pathology, University Medical Center Göttingen, Georg-August-University, 37075, Göttingen, Germany
Fernandez-Florido E:: Division Vascular Signaling and Cancer, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany
Mülfarth R:: Division Vascular Signaling and Cancer, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany

Faculty of Biosciences, University of Heidelberg, 69120, Heidelberg, Germany
Vacca M:: Division Vascular Signaling and Cancer, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany
Gerwing J:: Division Vascular Signaling and Cancer, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany
Conradi LC:: Clinic of General, Visceral and Pediatric Surgery, University Medical Center Göttingen, Robert-Koch-Straße 40, 37075, Göttingen, Germany
Ströbel P:: Institute of Pathology, University Medical Center Göttingen, Georg-August-University, 37075, Göttingen, Germany
Trumpp A:: Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany

HI-STEM - Heidelberg Institute for Stem Cell Technology and Experimental Medicine gGmbH, 69120, Heidelberg, Germany
Mogler C:: Institute of Pathology, Technical University of Munich, 81675, Munich, Germany
Fischer A:: Division Vascular Signaling and Cancer, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.

Institute for Clinical Chemistry, University Medical Center Göttingen, 37075, Göttingen, Germany.

German Center for Cardiovascular Research (DZHK), partner site Göttingen, Germany.
Rodriguez-Vita J:: Tumor-Stroma Communication Laboratory, Centro de Investigación Príncipe Felipe, 46012, Valencia, Spain.

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