TNFR1 mediates TNF-α-induced tumour lymphangiogenesis and metastasis by modulating VEGF-C-VEGFR3 signalling

Hong Ji, Renhai Cao, Yunlong Yang, Yin Zhang, Hideki Iwamoto, Sharon Lim, Masaki Nakamura, Patrik Andersson, Jian Wang, Yuping Sun, Steen Dissing, Xia He, Xiaojuan Yang and Yihai Cao ()
Additional contact information
Hong Ji: Tumor and Cell Biology, Karolinska Institute
Renhai Cao: Tumor and Cell Biology, Karolinska Institute
Yunlong Yang: Tumor and Cell Biology, Karolinska Institute
Yin Zhang: Tumor and Cell Biology, Karolinska Institute
Hideki Iwamoto: Tumor and Cell Biology, Karolinska Institute
Sharon Lim: Tumor and Cell Biology, Karolinska Institute
Masaki Nakamura: Tumor and Cell Biology, Karolinska Institute
Patrik Andersson: Tumor and Cell Biology, Karolinska Institute
Jian Wang: Tumor and Cell Biology, Karolinska Institute
Yuping Sun: Jinan Central Hospital Affiliated to Shandong University, No.105, Jiefang Road
Steen Dissing: Panum Institute, University of Copenhagen
Xia He: Jiangsu Cancer Hospital Affiliated to Nanjing Medical University
Xiaojuan Yang: Tumor and Cell Biology, Karolinska Institute
Yihai Cao: Tumor and Cell Biology, Karolinska Institute

Nature Communications, 2014, vol. 5, issue 1, 1-17

Abstract: Abstract Inflammation and lymphangiogenesis are two cohesively coupled processes that promote tumour growth and invasion. Here we report that TNF-α markedly promotes tumour lymphangiogenesis and lymphatic metastasis. The TNF-α-TNFR1 signalling pathway directly stimulates lymphatic endothelial cell activity through a VEGFR3-independent mechanism. However, VEGFR3-induced lymphatic endothelial cell tips are a prerequisite for lymphatic vessel growth in vivo, and a VEGFR3 blockade completely ablates TNF-α-induced lymphangiogenesis. Moreover, TNF-α-TNFR1-activated inflammatory macrophages produce high levels of VEGF-C to coordinately activate VEGFR3. Genetic deletion of TNFR1 (Tnfr1−/−) in mice or depletion of tumour-associated macrophages (TAMs) virtually eliminates TNF-α-induced lymphangiogenesis and lymphatic metastasis. Gain-of-function experiments show that reconstitution of Tnfr1+/+ macrophages in Tnfr1−/− mice largely restores tumour lymphangiogenesis and lymphatic metastasis. These findings shed mechanistic light on the intimate interplay between inflammation and lymphangiogenesis in cancer metastasis, and propose therapeutic intervention of lymphatic metastasis by targeting the TNF-α-TNFR1 pathway.

Date: 2014
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms5944 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5944

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms5944

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().