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CD163, a novel therapeutic target, regulates the proliferation and stemness of glioma cells via casein kinase 2

Oncogenevolume 38pages11831199 (2019) | Download Citation

Abstract

Glioma is a devastating cancer with a dismal prognosis and there is an urgent need to discover novel glioma-specific antigens for glioma therapy. Previous studies have identified CD163-positive tumour cells in certain solid tumours, but CD163 expression in glioma remains unknown. In this study, via an analysis of public datasets, we demonstrated that CD163 overexpression in glioma specimens correlated with an unfavourable patient prognosis. CD163 expression was increased in glioma cells, especially primary glioma cells. The loss of CD163 expression inhibited both cell cycle progression and the proliferation of glioblastoma multiforme (GBM) cell lines and primary glioma cells. CD163 interacted directly with casein kinase 2 (CK2) and CD163 silencing reduced AKT/GSK3β/β-catenin/cyclin D1 pathway activity via CK2. Moreover, CD163 was upregulated in CD133-positive glioma stem cells (GSCs), and CD163 downregulation decreased the expression of GSC markers, including CD133, ALDH1A1, NANOG and OCT4. The knockdown of CD163 impaired GSC stemness by inhibiting the CK2/AKT/GSK3β/β-catenin pathway. Finally, a CD163 antibody successfully induced complement-dependent cytotoxicity against glioma cells. Our findings indicate that CD163 contributes to gliomagenesis via CK2 and provides preclinical evidence that CD163 and the CD163 pathway might serve as a therapeutic target for glioma.

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Additional information

These authors contributed equally: Taoliang Chen, Jiansheng Chen

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Acknowledgements

This work was supported by the Natural Science Foundation of China (nos. 81772651 and 81772652).

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    Affiliations

    1. The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, 510282, Guangzhou, China

      • Taoliang Chen
      • , Jiansheng Chen
      • , Yubo Zhu
      • , Yan Li
      • , Yun Wang
      • , Huajian Chen
      • , Jihui Wang
      • , Xiao Li
      • , Yang Liu
      • , Baisheng Li
      • , Xinlin Sun
      •  & Yiquan Ke
    2. Department of Neurosurgery, The First Hospital of Xinjiang Medical University, 830054, Urumqi, China

      • Yun Wang
    3. Department of Neurosurgery, Huizhou Central People’s Hospital, 516001, Huizhou, China

      • Baisheng Li

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    Correspondence to Xinlin Sun or Yiquan Ke.

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    https://doi.org/10.1038/s41388-018-0515-6