The PDGF-BB-SOX7 axis-modulated IL-33 in pericytes and stromal cells promotes metastasis through tumour-associated macrophages
Name
The PDGF-BB-SOX7.pdf
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3.65 MB
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Author(s)
Yang, Yunlong
Andersson, Patrik
Hosaka, Kayoko
Zhang, Yin
Cao, Renhai
Iwamoto, Hideki
Yang, Xiaojuan
Nakamura, Masaki
Wang, Jian
Zhuang, Rujie
Date Issued
May 2016
Journal
Nature Communications
Publisher
Nature Publishing Group
Citation
Yang, Yunlong et al. “The PDGF-BB-SOX7 Axis-Modulated IL-33 in Pericytes and Stromal Cells Promotes Metastasis through Tumour-Associated Macrophages.” Nature Communications 7 (2016): 11385.
Version
Final published version
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.
MIT Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Chemical Engineering
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Creative Commons Attribution 4.0 International License
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DOI of Published Version
https://doi.org/10.1038/ncomms11385
