The PDGF-BB-SOX7 axis-modulated IL-33 in pericytes and stromal cells promotes metastasis through tumour-associated macrophages

Yunlong Yang, Patrik Andersson, Kayoko Hosaka, Yin Zhang, Renhai Cao, Hideki Iwamoto, Xiaojuan Yang, Masaki Nakamura, Jian Wang, Rujie Zhuang, Hiromasa Morikawa, Yuan Xue, Harald Braun, Rudi Beyaert, Nilesh Samani, Susumu Nakae, Emily Hams, Steen Dissing, Padraic G. Fallon, Robert Langer and Yihai Cao ()
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Yunlong Yang: Tumor and Cell Biology, Karolinska Institute
Patrik Andersson: Tumor and Cell Biology, Karolinska Institute
Kayoko Hosaka: Tumor and Cell Biology, Karolinska Institute
Yin Zhang: Tumor and Cell Biology, Karolinska Institute
Renhai Cao: Tumor and Cell Biology, Karolinska Institute
Hideki Iwamoto: Tumor and Cell Biology, Karolinska Institute
Xiaojuan Yang: Tumor and Cell Biology, Karolinska Institute
Masaki Nakamura: Tumor and Cell Biology, Karolinska Institute
Jian Wang: Tumor and Cell Biology, Karolinska Institute
Rujie Zhuang: The TCM Hospital of Zhejiang Province
Hiromasa Morikawa: Unit of Computational Medicine, Center for Molecular Medicine, Karolinska Institute
Yuan Xue: Tumor and Cell Biology, Karolinska Institute
Harald Braun: Ghent University
Rudi Beyaert: Ghent University
Nilesh Samani: University of Leicester and NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital
Susumu Nakae: Laboratory of Systems Biology, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo
Emily Hams: School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, College Green
Steen Dissing: Panum Institute, University of Copenhagen
Padraic G. Fallon: School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, College Green
Robert Langer: Institute for Medical Engineering and Science, Massachusetts Institute of Technology
Yihai Cao: Tumor and Cell Biology, Karolinska Institute

Nature Communications, 2016, vol. 7, issue 1, 1-18

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms11385

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