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

Author(s)
Yang, Yunlong; Andersson, Patrik; Hosaka, Kayoko; Zhang, Yin; Cao, Renhai; Iwamoto, Hideki; Yang, Xiaojuan; Nakamura, Masaki; Wang, Jian; Zhuang, Rujie; Morikawa, Hiromasa; Braun, Harald; Beyaert, Rudi; Samani, Nilesh; Nakae, Susumu; Hams, Emily; Dissing, Steen; Fallon, Padraic G.; Cao, Yihai; Xue, Yuan; Langer, Robert S; ... Show more Show less
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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 issued
2016-05
URI
http://hdl.handle.net/1721.1/110671
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
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
ISSN
2041-1723

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