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Title: The PDGF-BB-SOX7 axis-modulated IL-33 in pericytes and stromal cells promotes metastasis through tumour-associated macrophages
Authors: Yang, Yunlong
Andersson, Patrik
Hosaka, Kayoko
Zhang, Yin
Cao, Renhai
Iwamoto, Hideki
Yang, Xiaojuan
Nakamura, Masaki
Wang, Jian
Zhuang, Rujie
Morikawa, Hiromasa
Xue, Yuan
Braun, Harald
Beyaert, Rudi
Samani, Nilesh
Nakae, Susumu
Hams, Emily
Dissing, Steen
Fallon, Padraic G.
Langer, Robert
Cao, Yihai
First Published: 6-May-2016
Publisher: Nature Publishing Group
Citation: Nature Communications, 2016, 7, article number 11385
Abstract: 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.
DOI Link: 10.1038/ncomms11385
eISSN: 2041-1723
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © the authors, 2016. This is an open-access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Appears in Collections:Published Articles, Dept. of Cardiovascular Sciences

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