HAPLN1 potentiates peritoneal metastasis in pancreatic cancer.

Autor: 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-Straβe 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. andreas.fischer@med.uni-goettingen.de.; Institute for Clinical Chemistry, University Medical Center Göttingen, 37075, Göttingen, Germany. andreas.fischer@med.uni-goettingen.de.; German Center for Cardiovascular Research (DZHK), partner site Göttingen, Germany. andreas.fischer@med.uni-goettingen.de., Rodriguez-Vita J; Division Vascular Signaling and Cancer, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany. jrodriguez@cipf.es.; Tumor-Stroma Communication Laboratory, Centro de Investigación Príncipe Felipe, 46012, Valencia, Spain. jrodriguez@cipf.es.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Apr 24; Vol. 14 (1), pp. 2353. Date of Electronic Publication: 2023 Apr 24.
DOI: 10.1038/s41467-023-38064-w
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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