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

Author

Listed:
  • 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
    Institute for Medical Engineering and Science, Massachusetts Institute of Technology)

  • Harald Braun

    (Ghent University
    Unit of Molecular Signal Transduction in Inflammation, Inflammation Research Center VIB)

  • Rudi Beyaert

    (Ghent University
    Unit of Molecular Signal Transduction in Inflammation, Inflammation Research Center VIB)

  • 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
    University of Leicester and NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital
    Linköping University)

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.

Suggested Citation

  • 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 & R, 2016. "The PDGF-BB-SOX7 axis-modulated IL-33 in pericytes and stromal cells promotes metastasis through tumour-associated macrophages," Nature Communications, Nature, vol. 7(1), pages 1-18, September.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11385
    DOI: 10.1038/ncomms11385
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    Cited by:

    1. Xiaoting Sun & Wenhai Sui & Zepeng Mu & Sisi Xie & Jinxiu Deng & Sen Li & Takahiro Seki & Jieyu Wu & Xu Jing & Xingkang He & Yangang Wang & Xiaokun Li & Yunlong Yang & Ping Huang & Minghua Ge & Yihai , 2023. "Mirabegron displays anticancer effects by globally browning adipose tissues," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Olivia Le Saux & Maude Ardin & Justine Berthet & Sarah Barrin & Morgane Bourhis & Justine Cinier & Yasmine Lounici & Isabelle Treilleux & Pierre-Alexandre Just & Guillaume Bataillon & Aude-Marie Savoy, 2024. "Immunomic longitudinal profiling of the NeoPembrOv trial identifies drivers of immunoresistance in high-grade ovarian carcinoma," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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