Author
Listed:
- Lena Wiedmann
(German Cancer Research Center (DKFZ)
University of Heidelberg)
- Francesca De Angelis Rigotti
(German Cancer Research Center (DKFZ)
Centro de Investigación Príncipe Felipe)
- Nuria Vaquero-Siguero
(German Cancer Research Center (DKFZ))
- Elisa Donato
(German Cancer Research Center (DKFZ)
HI-STEM - Heidelberg Institute for Stem Cell Technology and Experimental Medicine gGmbH)
- Elisa Espinet
(German Cancer Research Center (DKFZ)
HI-STEM - Heidelberg Institute for Stem Cell Technology and Experimental Medicine gGmbH
University of Barcelona (UB), L’Hospitalet de Llobregat
L’Hospitalet de Llobregat)
- Iris Moll
(German Cancer Research Center (DKFZ))
- Elisenda Alsina-Sanchis
(German Cancer Research Center (DKFZ)
University Medical Center Göttingen)
- Hanibal Bohnenberger
(University Medical Center Göttingen, Georg-August-University)
- Elena Fernandez-Florido
(German Cancer Research Center (DKFZ))
- Ronja Mülfarth
(German Cancer Research Center (DKFZ)
University of Heidelberg)
- Margherita Vacca
(German Cancer Research Center (DKFZ))
- Jennifer Gerwing
(German Cancer Research Center (DKFZ))
- Lena-Christin Conradi
(University Medical Center Göttingen)
- Philipp Ströbel
(University Medical Center Göttingen, Georg-August-University)
- Andreas Trumpp
(German Cancer Research Center (DKFZ)
HI-STEM - Heidelberg Institute for Stem Cell Technology and Experimental Medicine gGmbH)
- Carolin Mogler
(Technical University of Munich)
- Andreas Fischer
(German Cancer Research Center (DKFZ)
University Medical Center Göttingen
German Center for Cardiovascular Research (DZHK))
- Juan Rodriguez-Vita
(German Cancer Research Center (DKFZ)
Centro de Investigación Príncipe Felipe)
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.
Suggested Citation
Lena Wiedmann & Francesca De Angelis Rigotti & Nuria Vaquero-Siguero & Elisa Donato & Elisa Espinet & Iris Moll & Elisenda Alsina-Sanchis & Hanibal Bohnenberger & Elena Fernandez-Florido & Ronja Mülfa, 2023.
"HAPLN1 potentiates peritoneal metastasis in pancreatic cancer,"
Nature Communications, Nature, vol. 14(1), pages 1-18, December.
Handle:
RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38064-w
DOI: 10.1038/s41467-023-38064-w
Download full text from publisher
Most related items
These are the items that most often cite the same works as this one and are cited by the same works as this one.
- Xiaoyu Liu & Yaping Zhuang & Wei Huang & Zhuozhuo Wu & Yingjie Chen & Qungang Shan & Yuefang Zhang & Zhiyuan Wu & Xiaoyi Ding & Zilong Qiu & Wenguo Cui & Zhongmin Wang, 2023.
"Interventional hydrogel microsphere vaccine as an immune amplifier for activated antitumour immunity after ablation therapy,"
Nature Communications, Nature, vol. 14(1), pages 1-19, December.
- Manuel Rodrigues & Giulia Vanoni & Pierre Loap & Coraline Dubot & Eleonora Timperi & Mathieu Minsat & Louis Bazire & Catherine Durdux & Virginie Fourchotte & Enora Laas & Nicolas Pouget & Zahra Castel, 2023.
"Nivolumab plus chemoradiotherapy in locally-advanced cervical cancer: the NICOL phase 1 trial,"
Nature Communications, Nature, vol. 14(1), pages 1-15, December.
Corrections
All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38064-w. See general information about how to correct material in RePEc.
If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.
If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .
If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.
For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .
Please note that corrections may take a couple of weeks to filter through
the various RePEc services.