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ADAMTS1 as potential prognostic biomarker promotes malignant invasion of glioma

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Abstract

Background

Glioma is the most common intracranial malignancy in adults with a high degree of malignancy and poor prognosis, which is largely attributed to the existence of glioma stem cells (GSCs). Previous evidence indicated that the matrix metalloproteinase ADAMTS1 was implicated in the process of tumor invasion, but the involvement of ADAMTS1 in glioma malignant invasion remains poorly understood.

Methods

The expression and prognosis values of ADAMTS1 were investigated in patients with glioma based on ONCOMINE and GEPIA databases. ADAMTS1 expression of different malignancy grade tissues was determined by immunohistochemistry. The effects of ADAMTS1 on cell proliferation and invasion were determined by clone formation assay and Transwell migration assay. The animal experiment was performed in an intracranial orthotopic xenograft model by knockout of ADAMTS1. Stemness properties and Notch1-SOX2 pathway were examined in stable ADAMTS1 knockdown GSCs.

Results

The expression levels of ADAMTS1 were significantly higher in glioma tissues and significantly correlated with the grade of malignancy and prognosis of glioma. Elevated ADAMTS1 expression was associated with SOX2, N-cadherin and the resistance of chemoradiotherapy of glioma patients. ADAMTS1 knockout suppressed the intracranial orthotopic xenograft growth and prolonged the survival of xenograft mice in vivo. Mechanistically, we found a blockade of the migration and invasiveness of GSCs and the expression levels of Notch1 and SOX2 in absence of ADAMTS1.

Conclusion

As a biomarker for prediction of prognosis, ADAMTS1 may affect the invasive phenotype of GSCs by regulating Notch1-SOX2 signaling pathway, thereby promoting the invasive growth of glioma.

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Data availability

The datasets generated during and analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This work was supported by Tianjin Natural Science Foundation (grant number: 21JCQNJC01610), National Natural Science Foundation of China (grant number: 82003134), Natural Science Foundation of Beijing Municipality (grant number: 7222053), China Postdoctoral Science Foundation (grant number: 2020M670382, 2019T120115), Beijing Financial Support for Postdoctoral Research (grant number: ZZ2019-08) and Tianjin Key Medical Discipline (Specialty) Construction Project (grant number: TJYXZDXK-009A).

Author information

Author notes

  1. Shanshan Wang and Jin Zhang have contributed equally to this work. Yuanli Zhao and Dongying Liu represented as senior authors.

Authors and Affiliations

  1. Department of Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China

    Shanshan Wang & Dongying Liu

  2. Tianjin’s Clinical Research Center for Cancer, Tianjin, China

    Shanshan Wang & Dongying Liu

  3. Key Laboratory of Cancer Prevention and Therapy, Tianjin, China

    Shanshan Wang & Dongying Liu

  4. Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

    Jin Zhang, Ke Wang & Yuanli Zhao

  5. Stoke Center, Beijing Institute for Brain Disorders, Beijing, China

    Jin Zhang, Ke Wang & Yuanli Zhao

  6. Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China

    Jin Zhang, Ke Wang & Yuanli Zhao

  7. China National Clinical Research Center for Neurological Diseases, Beijing, China

    Jin Zhang, Ke Wang & Yuanli Zhao

Authors
  1. Shanshan Wang
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  2. Jin Zhang
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  3. Ke Wang
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  4. Yuanli Zhao
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  5. Dongying Liu
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Contributions

All authors contributed to the study conception and design. Material, preparation, data collection and analysis were performed by SW, JZ, KW, YZ, DL. The first draft of the manuscript was written by SW and JZ and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Yuanli Zhao or Dongying Liu.

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Wang, S., Zhang, J., Wang, K. et al. ADAMTS1 as potential prognostic biomarker promotes malignant invasion of glioma. Int J Clin Oncol 28, 52–68 (2023). https://doi.org/10.1007/s10147-022-02268-9

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  • DOI: https://doi.org/10.1007/s10147-022-02268-9

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