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Exosomal EphA2 promotes tumor metastasis of triple-negative breast cancer by damaging endothelial barrier

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Abstract

Many evidences show that exosomes play an important role in cancer development, invasion and metastasis. This study is based on the need to explore exosomal protein that promote breast cancer metastasis. We found that tyrosine kinase EphA2 was enriched in Triple-negative breast cancer -derived exosomes and it could disrupt the endothelial monolayer barrier through downregulating tight junction proteins of endothelial cells. These mechanisms were confirmed by in vivo experiments. After periodical injection of exosomal EphA2 into mice caudal vein, we found increased vascular permeability and breast cancer metastases in distant organs, and this phenomenon decreased dramatically after exosomal EphA2 knockdown. This study provides a new mechanism of exosome promoting breast cancer metastasis and suggests a new therapeutic target for the prevention and treatment of breast cancer metastasis.

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Data availability

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

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Acknowledgements

Not applicable.

Funding

This work was supported by Xiamen Key Laboratory of Endocrine-Related Cancer Precision Medicine (XKLEC2021KF02), the Young and Middle-aged Talents Training Program of Fujian Provincial Health Commission (2020GGB062), Natural Science Foundation of Fujian Province (2019J01012) and Scientific Research Foundation for Advanced Talents, Xiang’an Hospital of Xiamen University (PM201809170014).

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Authors and Affiliations

  1. Department of Oncology, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361102, Fujian, China

    Xin Liu, Yue Li, Jie Zhou, Lei Wang & Xinmei Kang

  2. State Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences, Xiamen University, Xiamen, 361102, Fujian, China

    Chunjing Chen & Xiang Gao

  3. Department of Electronic Science, National Institute for Data Science in Health and Medicine, Xiamen University, Xiamen, 361102, Fujian, China

    Jiyang Dong

  4. School of Medicine, Huaqiao University, Xiamen, 362021, Fujian, China

    Dandan Tong

Authors
  1. Xin Liu
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  2. Yue Li
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  9. Xinmei Kang
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Contributions

XMK and XG conceived and designed the experiments. XL, YL, CJC and JZ performed the experiments. JYD, DDT and LW analyzed and interpreted the data. XL wrote the original manuscript, XG and XMK edited and revised the manuscript, and all authors reviewed the manuscript and approved of the final version.

Corresponding authors

Correspondence to Xiang Gao or Xinmei Kang.

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Competing interests

The authors declare that they have no competing interests.

Ethical approval

All animal experiments were approved by Laboratory Animal Management and Ethics Committee of Xiamen University (Fujian, China).

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Supplementary Information

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10585_2022_10194_MOESM1_ESM.pdf

Supplementary file1 (PDF 71 kb)— Figure S1. Analysis of exosomal proteins derived from breast cancer cell lines by using mass spectrometry. (A) Venn diagram of proteins derived from MCF-7 exosomes with 2 replications; (B) &(C) GO enrichment analysis of exosomal proteins of MDA-MB-231, MCF-10A and MCF-7 cell lines. MF: Molecular function; CC: Cellular component.

Supplementary file2 (DOCX 16 kb)

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Liu, X., Li, Y., Chen, C. et al. Exosomal EphA2 promotes tumor metastasis of triple-negative breast cancer by damaging endothelial barrier. Clin Exp Metastasis 40, 105–116 (2023). https://doi.org/10.1007/s10585-022-10194-3

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  • DOI: https://doi.org/10.1007/s10585-022-10194-3

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