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Fibrocyte-like cells mediate acquired resistance to anti-angiogenic therapy with bevacizumab

Author

Listed:
  • Atsushi Mitsuhashi

    (Institute of Biomedical Sciences, Tokushima University Graduate School)

  • Hisatsugu Goto

    (Institute of Biomedical Sciences, Tokushima University Graduate School)

  • Atsuro Saijo

    (Institute of Biomedical Sciences, Tokushima University Graduate School)

  • Van The Trung

    (Institute of Biomedical Sciences, Tokushima University Graduate School)

  • Yoshinori Aono

    (Institute of Biomedical Sciences, Tokushima University Graduate School)

  • Hirokazu Ogino

    (Institute of Biomedical Sciences, Tokushima University Graduate School)

  • Takuya Kuramoto

    (Institute of Biomedical Sciences, Tokushima University Graduate School)

  • Sho Tabata

    (Institute of Biomedical Sciences, Tokushima University Graduate School)

  • Hisanori Uehara

    (Institute of Biomedical Sciences, Tokushima University Graduate School)

  • Keisuke Izumi

    (Institute of Biomedical Sciences, Tokushima University Graduate School)

  • Mitsuteru Yoshida

    (Endocrine Surgery and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School)

  • Hiroaki Kobayashi

    (Fukui-ken Saiseikai Hospital)

  • Hidefusa Takahashi

    (Municipal Tsuruga Hospital)

  • Masashi Gotoh

    (Breast and Endocrinological Surgery, Faculty of Medicine, Kagawa University)

  • Soji Kakiuchi

    (Institute of Biomedical Sciences, Tokushima University Graduate School)

  • Masaki Hanibuchi

    (Institute of Biomedical Sciences, Tokushima University Graduate School)

  • Seiji Yano

    (Cancer Research Institute, Kanazawa University)

  • Hiroyasu Yokomise

    (Breast and Endocrinological Surgery, Faculty of Medicine, Kagawa University)

  • Shoji Sakiyama

    (Endocrine Surgery and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School)

  • Yasuhiko Nishioka

    (Institute of Biomedical Sciences, Tokushima University Graduate School
    JST, CREST)

Abstract

Bevacizumab exerts anti-angiogenic effects in cancer patients by inhibiting vascular endothelial growth factor (VEGF). However, its use is still limited due to the development of resistance to the treatment. Such resistance can be regulated by various factors, although the underlying mechanisms remain incompletely understood. Here we show that bone marrow-derived fibrocyte-like cells, defined as alpha-1 type I collagen-positive and CXCR4-positive cells, contribute to the acquired resistance to bevacizumab. In mouse models of malignant pleural mesothelioma and lung cancer, fibrocyte-like cells mediate the resistance to bevacizumab as the main producer of fibroblast growth factor 2. In clinical specimens of lung cancer, the number of fibrocyte-like cells is significantly increased in bevacizumab-treated tumours, and correlates with the number of treatment cycles, as well as CD31-positive vessels. Our results identify fibrocyte-like cells as a promising cell biomarker and a potential therapeutic target to overcome resistance to anti-VEGF therapy.

Suggested Citation

  • Atsushi Mitsuhashi & Hisatsugu Goto & Atsuro Saijo & Van The Trung & Yoshinori Aono & Hirokazu Ogino & Takuya Kuramoto & Sho Tabata & Hisanori Uehara & Keisuke Izumi & Mitsuteru Yoshida & Hiroaki Koba, 2015. "Fibrocyte-like cells mediate acquired resistance to anti-angiogenic therapy with bevacizumab," Nature Communications, Nature, vol. 6(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9792
    DOI: 10.1038/ncomms9792
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    Cited by:

    1. Andreas Weigert & Xiang Zheng & Alina Nenzel & Kati Turkowski & Stefan Günther & Elisabeth Strack & Evelyn Sirait-Fischer & Eiman Elwakeel & Ivan M. Kur & Vandana S. Nikam & Chanil Valasarajan & Hauke, 2022. "Fibrocytes boost tumor-supportive phenotypic switches in the lung cancer niche via the endothelin system," Nature Communications, Nature, vol. 13(1), pages 1-21, December.

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