liu.seSearch for publications in DiVA
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
TNFR1 mediates TNF-alpha-induced tumour lymphangiogenesis and metastasis by modulating VEGF-C-VEGFR3 signalling
Karolinska Institute, Sweden; Nanjing Medical University, Peoples R China.
Karolinska Institute, Sweden.
Karolinska Institute, Sweden.
Karolinska Institute, Sweden.
Show others and affiliations
2014 (English)In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 5, no 4944Article in journal (Refereed) Published
Abstract [en]

Inflammation and lymphangiogenesis are two cohesively coupled processes that promote tumour growth and invasion. Here we report that TNF-alpha markedly promotes tumour lymphangiogenesis and lymphatic metastasis. The TNF-alpha-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-alpha-induced lymphangiogenesis. Moreover, TNF-alpha-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-alpha-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-alpha-TNFR1 pathway.

Place, publisher, year, edition, pages
Nature Publishing Group: Nature Communications , 2014. Vol. 5, no 4944
National Category
Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-120670DOI: 10.1038/ncomms5944ISI: 000358590800001PubMedID: 25229256OAI: oai:DiVA.org:liu-120670DiVA: diva2:847525
Note

Funding Agencies|Swedish Research Council; Swedish Cancer Foundation; Karolinska Institute Foundation; Karolinska Institute; Torsten Soderbergs foundation; Soderbergs stiftelse; Tianjin Natural Science Foundation (CMM-Tianjin) [09ZCZDSF04400]; European Union [222741]; European Research Council (ERC) advanced grant ANGIOFAT [250021]

Available from: 2015-08-20 Created: 2015-08-20 Last updated: 2017-12-04

Open Access in DiVA

fulltext(4685 kB)182 downloads
File information
File name FULLTEXT01.pdfFile size 4685 kBChecksum SHA-512
9de09cdecbbc3dd5f28d1e243787e425b5eb68729be115ed001de12050355c9cfa475352d5a0511f272afa7b7b96fb09ff3e117ae2f6f057f612ad6d1db45d93
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Authority records BETA

Cao, Yihai

Search in DiVA

By author/editor
Cao, Yihai
By organisation
Department of Medical and Health SciencesFaculty of Medicine and Health Sciences
In the same journal
Nature Communications
Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
Total: 182 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 103 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf