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Dual blockade of CD47 and HER2 eliminates radioresistant breast cancer cells

Author

Listed:
  • Demet Candas-Green

    (University of California Davis)

  • Bowen Xie

    (University of California Davis
    Xiangya Hospital, Central South University)

  • Jie Huang

    (University of California Davis)

  • Ming Fan

    (University of California Davis)

  • Aijun Wang

    (University of California Davis)

  • Cheikh Menaa

    (University of California Davis)

  • Yanhong Zhang

    (Kaiser Permanente Medical Center Vallejo and Vacaville)

  • Lu Zhang

    (University of California Davis
    Xiangya Hospital, Central South University)

  • Di Jing

    (University of California Davis
    Xiangya Hospital, Central South University)

  • Soheila Azghadi

    (University of California Davis)

  • Weibing Zhou

    (University of California Davis
    Xiangya Hospital, Central South University)

  • Lin Liu

    (University of California Davis)

  • Nian Jiang

    (University of California Davis)

  • Tao Li

    (University of California Davis)

  • Tianyi Gao

    (University of California Davis)

  • Colleen Sweeney

    (University of California Davis
    University of California Davis)

  • Rulong Shen

    (Ohio State University)

  • Tzu-yin Lin

    (University of California Davis)

  • Chong-xian Pan

    (University of California Davis
    University of California Davis)

  • Omer M. Ozpiskin

    (University of California Davis)

  • Gayle Woloschak

    (Northwestern University, Feinberg School of Medicine)

  • David J. Grdina

    (The University of Chicago)

  • Andrew T. Vaughan

    (University of California Davis
    University of California Davis)

  • Ji Ming Wang

    (Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute)

  • Shuli Xia

    (Johns Hopkins School of Medicine)

  • Arta M. Monjazeb

    (University of California Davis
    University of California Davis)

  • William J. Murphy

    (University of California Davis
    University of California Davis)

  • Lun-Quan Sun

    (Xiangya Hospital, Central South University)

  • Hong-Wu Chen

    (University of California Davis
    University of California Davis)

  • Kit S. Lam

    (University of California Davis
    University of California Davis)

  • Ralph R. Weichselbaum

    (The University of Chicago)

  • Jian Jian Li

    (University of California Davis
    University of California Davis)

Abstract

Although the efficacy of cancer radiotherapy (RT) can be enhanced by targeted immunotherapy, the immunosuppressive factors induced by radiation on tumor cells remain to be identified. Here, we report that CD47-mediated anti-phagocytosis is concurrently upregulated with HER2 in radioresistant breast cancer (BC) cells and RT-treated mouse syngeneic BC. Co-expression of both receptors is more frequently detected in recurrent BC patients with poor prognosis. CD47 is upregulated preferentially in HER2-expressing cells, and blocking CD47 or HER2 reduces both receptors with diminished clonogenicity and augmented phagocytosis. CRISPR-mediated CD47 and HER2 dual knockouts not only inhibit clonogenicity but also enhance macrophage-mediated attack. Dual antibody of both receptors synergizes with RT in control of syngeneic mouse breast tumor. These results provide the evidence that aggressive behavior of radioresistant BC is caused by CD47-mediated anti-phagocytosis conjugated with HER2-prompted proliferation. Dual blockade of CD47 and HER2 is suggested to eliminate resistant cancer cells in BC radiotherapy.

Suggested Citation

  • Demet Candas-Green & Bowen Xie & Jie Huang & Ming Fan & Aijun Wang & Cheikh Menaa & Yanhong Zhang & Lu Zhang & Di Jing & Soheila Azghadi & Weibing Zhou & Lin Liu & Nian Jiang & Tao Li & Tianyi Gao & C, 2020. "Dual blockade of CD47 and HER2 eliminates radioresistant breast cancer cells," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18245-7
    DOI: 10.1038/s41467-020-18245-7
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