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

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  • ncomms11385

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  • 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
  • Padraic G Fallon
  • Robert Langer
  • Yihai Cao
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.
OriginalsprogEngelsk
TidsskriftNature Communications
Vol/bind7
Sider (fra-til)11385
ISSN2041-1723
DOI
StatusUdgivet - 2016

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