Change search
ReferencesLink to record
Permanent link

Direct link
The PDGF-BB-SOX7 axis-modulated IL-33 in pericytes and stromal cells promotes metastasis through tumour-associated macrophages
Karolinska Institute, Sweden.
Karolinska Institute, Sweden.
Karolinska Institute, Sweden.
Karolinska Institute, Sweden.
Show others and affiliations
2016 (English)In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 7, no 11385Article in journal (Refereed) PublishedText
Abstract [en]

Signalling molecules and pathways that mediate crosstalk between various tumour cellular compartments in cancer metastasis remain largely unknown. We report a mechanism of the interaction between perivascular cells and tumour-associated macrophages (TAMs) in promoting metastasis through the IL-33-ST2-dependent pathway in xenograft mouse models of cancer. IL-33 is the highest upregulated gene through activation of SOX7 transcription factor in PDGF-BB-stimulated pericytes. Gain-and loss-of-function experiments validate that IL-33 promotes metastasis through recruitment of TAMs. Pharmacological inhibition of the IL-33-ST2 signalling by a soluble ST2 significantly inhibits TAMs and metastasis. Genetic deletion of host IL-33 in mice also blocks PDGF-BB-induced TAM recruitment and metastasis. These findings shed light on the role of tumour stroma in promoting metastasis and have therapeutic implications for cancer therapy.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP , 2016. Vol. 7, no 11385
National Category
Basic Medicine
URN: urn:nbn:se:liu:diva-128743DOI: 10.1038/ncomms11385ISI: 000375491600001PubMedID: 27150562OAI: diva2:931958

Funding Agencies|Swedish Research Council; Swedish Cancer Foundation; Karolinska Institute Foundation; Karolinska Institute distinguished professor award; Torsten Soderbergs foundation; Tore Nilsons foundation; Martin Rinds foundation; European Research Council (ERC) advanced grant ANGIOFAT [250021]; NOVO Nordisk Foundation

Available from: 2016-05-31 Created: 2016-05-30 Last updated: 2016-06-21

Open Access in DiVA

fulltext(3772 kB)10 downloads
File information
File name FULLTEXT01.pdfFile size 3772 kBChecksum SHA-512
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Search in DiVA

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

Search outside of DiVA

GoogleGoogle Scholar
Total: 10 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

Altmetric score

Total: 22 hits
ReferencesLink to record
Permanent link

Direct link