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Cancer cell-secreted IGF2 instigates fibroblasts and bone marrow-derived vascular progenitor cells to promote cancer progression

Author

Listed:
  • Wen Wen Xu

    (School of Biomedical Sciences, Li Ka Shing Faculty of Medicine
    The University of Hong Kong-Shenzhen Institute of Research and Innovation (HKU-SIRI)
    Present address: Institute of Tumor Pharmacology, College of Pharmacy, Jinan University, 601 West Huangpu Blvd., Guangzhou 510632, China)

  • Bin Li

    (School of Biomedical Sciences, Li Ka Shing Faculty of Medicine
    The University of Hong Kong-Shenzhen Institute of Research and Innovation (HKU-SIRI)
    Centre for Cancer Research, Li Ka Shing Faculty of Medicine
    Present address: College of Life Science and Technology, Jinan University, 601 West Huangpu Blvd., Guangzhou 510632, China)

  • Xin Yuan Guan

    (Centre for Cancer Research, Li Ka Shing Faculty of Medicine
    Li Ka Shing Faculty of Medicine)

  • Sookja K. Chung

    (School of Biomedical Sciences, Li Ka Shing Faculty of Medicine)

  • Yang Wang

    (College of Life Science and Technology, Jinan University)

  • Yim Ling Yip

    (School of Biomedical Sciences, Li Ka Shing Faculty of Medicine)

  • Simon Y. K. Law

    (Centre for Cancer Research, Li Ka Shing Faculty of Medicine
    Li Ka Shing Faculty of Medicine)

  • Kin Tak Chan

    (Centre for Cancer Research, Li Ka Shing Faculty of Medicine
    Li Ka Shing Faculty of Medicine)

  • Nikki P. Y. Lee

    (Centre for Cancer Research, Li Ka Shing Faculty of Medicine
    Li Ka Shing Faculty of Medicine)

  • Kwok Wah Chan

    (Centre for Cancer Research, Li Ka Shing Faculty of Medicine
    Li Ka Shing Faculty of Medicine)

  • Li Yan Xu

    (The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College)

  • En Min Li

    (The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College)

  • Sai Wah Tsao

    (School of Biomedical Sciences, Li Ka Shing Faculty of Medicine
    Centre for Cancer Research, Li Ka Shing Faculty of Medicine)

  • Qing-Yu He

    (College of Life Science and Technology, Jinan University)

  • Annie L. M. Cheung

    (School of Biomedical Sciences, Li Ka Shing Faculty of Medicine
    The University of Hong Kong-Shenzhen Institute of Research and Innovation (HKU-SIRI)
    Centre for Cancer Research, Li Ka Shing Faculty of Medicine)

Abstract

Local interactions between cancer cells and stroma can produce systemic effects on distant organs to govern cancer progression. Here we show that IGF2 secreted by inhibitor of differentiation (Id1)-overexpressing oesophageal cancer cells instigates VEGFR1-positive bone marrow cells in the tumour macroenvironment to form pre-metastatic niches at distant sites by increasing VEGF secretion from cancer-associated fibroblasts. Cancer cells are then attracted to the metastatic site via the CXCL5/CXCR2 axis. Bone marrow cells transplanted from nude mice bearing Id1-overexpressing oesophageal tumours enhance tumour growth and metastasis in recipient mice, whereas systemic administration of VEGFR1 antibody abrogates these effects. Mechanistically, IGF2 regulates VEGF in fibroblasts via miR-29c in a p53-dependent manner. Analysis of patient serum samples showed that concurrent elevation of IGF2 and VEGF levels may serve as a prognostic biomarker for oesophageal cancer. These findings suggest that the Id1/IGF2/VEGF/VEGFR1 cascade plays a critical role in tumour-driven pathophysiological processes underlying cancer progression.

Suggested Citation

  • Wen Wen Xu & Bin Li & Xin Yuan Guan & Sookja K. Chung & Yang Wang & Yim Ling Yip & Simon Y. K. Law & Kin Tak Chan & Nikki P. Y. Lee & Kwok Wah Chan & Li Yan Xu & En Min Li & Sai Wah Tsao & Qing-Yu He , 2017. "Cancer cell-secreted IGF2 instigates fibroblasts and bone marrow-derived vascular progenitor cells to promote cancer progression," Nature Communications, Nature, vol. 8(1), pages 1-17, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14399
    DOI: 10.1038/ncomms14399
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