The PDGF-BB-SOX7 axis-modulated IL-33 in pericytes and stromal cells promotes metastasis through tumour-associated macrophages
2016 (English)In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 7, no 11385Article in journal (Refereed) PublishedText
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
IdentifiersURN: urn:nbn:se:liu:diva-128743DOI: 10.1038/ncomms11385ISI: 000375491600001PubMedID: 27150562OAI: oai:DiVA.org:liu-128743DiVA: 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 ; NOVO Nordisk Foundation2016-05-312016-05-302016-06-21