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Dual Role of WISP1 in maintaining glioma stem cells and tumor-supportive macrophages in glioblastoma

Author

Listed:
  • Weiwei Tao

    (Lerner Research Institute, Cleveland Clinic)

  • Chengwei Chu

    (Lerner Research Institute, Cleveland Clinic)

  • Wenchao Zhou

    (Lerner Research Institute, Cleveland Clinic)

  • Zhi Huang

    (Lerner Research Institute, Cleveland Clinic)

  • Kui Zhai

    (Lerner Research Institute, Cleveland Clinic)

  • Xiaoguang Fang

    (Lerner Research Institute, Cleveland Clinic)

  • Qian Huang

    (Lerner Research Institute, Cleveland Clinic)

  • Aili Zhang

    (Lerner Research Institute, Cleveland Clinic)

  • Xiuxing Wang

    (University of California, San Diego)

  • Xingjiang Yu

    (Lerner Research Institute, Cleveland Clinic)

  • Haidong Huang

    (Lerner Research Institute, Cleveland Clinic)

  • Qiulian Wu

    (University of California, San Diego)

  • Andrew E. Sloan

    (University Hospitals, Case Western Reserve University
    Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine)

  • Jennifer S. Yu

    (Lerner Research Institute, Cleveland Clinic
    Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine
    Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic
    Center for Cancer Stem Cell Research, Lerner Research Institute, Cleveland Clinic)

  • Xiaoxia Li

    (Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine
    Lerner Research Institute, Cleveland Clinic)

  • George R. Stark

    (Lerner Research Institute, Cleveland Clinic
    Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine)

  • Jeremy N. Rich

    (University of California, San Diego)

  • Shideng Bao

    (Lerner Research Institute, Cleveland Clinic
    Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine
    Center for Cancer Stem Cell Research, Lerner Research Institute, Cleveland Clinic)

Abstract

The interplay between glioma stem cells (GSCs) and the tumor microenvironment plays crucial roles in promoting malignant growth of glioblastoma (GBM), the most lethal brain tumor. However, the molecular mechanisms underlying this crosstalk are incompletely understood. Here, we show that GSCs secrete the Wnt‐induced signaling protein 1 (WISP1) to facilitate a pro-tumor microenvironment by promoting the survival of both GSCs and tumor-associated macrophages (TAMs). WISP1 is preferentially expressed and secreted by GSCs. Silencing WISP1 markedly disrupts GSC maintenance, reduces tumor-supportive TAMs (M2), and potently inhibits GBM growth. WISP1 signals through Integrin α6β1-Akt to maintain GSCs by an autocrine mechanism and M2 TAMs through a paracrine manner. Importantly, inhibition of Wnt/β-catenin-WISP1 signaling by carnosic acid (CA) suppresses GBM tumor growth. Collectively, these data demonstrate that WISP1 plays critical roles in maintaining GSCs and tumor-supportive TAMs in GBM, indicating that targeting Wnt/β-catenin-WISP1 signaling may effectively improve GBM treatment and the patient survival.

Suggested Citation

  • Weiwei Tao & Chengwei Chu & Wenchao Zhou & Zhi Huang & Kui Zhai & Xiaoguang Fang & Qian Huang & Aili Zhang & Xiuxing Wang & Xingjiang Yu & Haidong Huang & Qiulian Wu & Andrew E. Sloan & Jennifer S. Yu, 2020. "Dual Role of WISP1 in maintaining glioma stem cells and tumor-supportive macrophages in glioblastoma," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16827-z
    DOI: 10.1038/s41467-020-16827-z
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    Cited by:

    1. Brijesh Kumar & Aditi S. Khatpe & Jiang Guanglong & Katie Batic & Poornima Bhat-Nakshatri & Maggie M. Granatir & Rebekah Joann Addison & Megan Szymanski & Lee Ann Baldridge & Constance J. Temm & Georg, 2023. "Stromal heterogeneity may explain increased incidence of metaplastic breast cancer in women of African descent," Nature Communications, Nature, vol. 14(1), pages 1-22, December.

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