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TRPS1 knockdown inhibits angiogenic vascular mimicry in human triple negative breast cancer cells

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Abstract

Purpose

Vascular mimicry (VM) tubules are lumen structures comprised of malignant tumor cells without the participation of endothelial cells. VM simulates blood vessel function in tumors to deliver a sufficient blood supply for proliferation, invasion, and metastasis of malignant tumors, thereby reducing the clinical effects of anti-angiogenic treatments. The elimination or prevention of malignant tumor VM development therefore represents an urgent research goal as a therapeutic strategy to and cut off nutrients required for tumor growth. The GATA transcription factor TRPS1 is abnormally up-regulated in breast cancer, osteosarcoma, prostate cancer, and other tumor tissues, and is instrumental in regulating cell proliferation, differentiation, and tissue growth and development.

Methods

Here, we explored the effects of TRPS1 knockdown on VM and the proteins underlying its development in triple-negative breast cancer cell line MDA-MB-231.

Results

We found that TRPS1 knockdown resulted in obvious inhibition of VM development. Fluorescence microscopy of F-actin and tubulin revealed that loss of TRPS1 function resulted in disruption of cytoskeleton and microtubule formation, respectively. In addition, TRPS1-suppressed cells exhibited reduced accumulation of VM-associated proteins EphA2, MMP-2, MMP-9, VEGF, and VE-cadherin. Moreover, it is interesting to know that the capacity for migration and invasion were limited in MDA-MB-231cells after TRPS1 knockdown and that the average number of VM tubules, their length, and number of intersections were also significantly decreased.

Conclusions

Based on our results, and in light of previous studies, we thus proposed that TRPS1 suppression negatively affects vascular mimicry possibly through reduced TRPS1-mediated transcriptional regulation of VM-related protein VEGF-A.

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Funding

This study was supported by The National Natural Science Foundation of China (No. 81673908).

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Authors and Affiliations

  1. Chinese Integrative Medicine Oncology Department, The First Affiliated Hospital of Anhui Medical University, No. 120 Wanshui Road, Shushan District, Hefei, 230022, Anhui Province, China

    M. Wu, X. Sun, T. Wang, M. Zhang & P. Li

Authors
  1. M. Wu
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  2. X. Sun
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  3. T. Wang
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  4. M. Zhang
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  5. P. Li
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Contributions

MW conceived and designed the study, and drafted the manuscript. XS and TW collected, analyzed and interpreted the experimental data. MZ and PL revised the manuscript for important intellectual content. All authors read and approved the final manuscript.

Corresponding author

Correspondence to P. Li.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study was approved by Ethical Committee of the First Affiliated Hospital of Anhui Medical University and conducted in accordance with the ethical standards.

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Wu, M., Sun, X., Wang, T. et al. TRPS1 knockdown inhibits angiogenic vascular mimicry in human triple negative breast cancer cells. Clin Transl Oncol 24, 145–153 (2022). https://doi.org/10.1007/s12094-021-02676-9

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  • DOI: https://doi.org/10.1007/s12094-021-02676-9

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