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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.
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2016 (English)In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 7, no 11385Article in journal (Refereed) Published
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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
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Basic Medicine
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URN: urn:nbn:se:liu:diva-128743DOI: 10.1038/ncomms11385ISI: 000375491600001PubMedID: 27150562OAI: oai:DiVA.org:liu-128743DiVA: diva2:931958
Note

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: 2017-11-30

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