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Breast cancer stem cells characterized by CD70 expression preferentially metastasize to the lungs

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Abstract

Background

Cancer stem cells (CSCs) are believed to form metastases. We sought to determine whether CD70 + subpopulation in human breast cancers represents the CSCs accounting for distant metastasis.

Methods

We measured the expression levels of CD70 in breast cancer cell lines and 122 primary breast cancer samples. We characterized the functional roles of CD70 + subpopulation in distant metastasis of breast cancers.

Results

We observed a distinct pattern of CD70 expression in a panel of primary breast carcinoma samples, indicating that CD70 serves as a biomarker of lung-specific metastasis. CD70− and CD70+ cell populations isolated from breast cancer cell lines exhibited epithelial and mesenchymal phenotypes, respectively. CD70+ cells, but not CD70− cells, possessed self-renewal and differentiation potentials. Tumorsphere formation in suspension cultures and in vivo tumorigenicity were significantly greater in CD70+ cells than in CD70− cells. Furthermore, the development of lung metastases induced by orthotopic injection was markedly increased in mice inoculated with CD70 + cells. CD70 contributed to the promotion of lung metastases by enhancing self-renewal potential of CD70 + cells.

Conclusions

We isolated CSCs from primary human breast cancers and found that CD70 + subpopulations mediate lung-specific metastasis. These findings might be used to aid in selection of patients for postoperative adjuvant therapy.

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Acknowledgements

This work was supported by grants from the National Nature Science Foundation of China (81372350, 81172099, 81572886 and 81501435).

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Author notes

  1. Li Liu, Bo Yin and Zhu Yi contributed equally to this manuscript.

Authors and Affiliations

  1. Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai, China

    Li Liu

  2. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China

    Li Liu

  3. Department of Radiology, HuaShan Hospital, Fudan University, Shanghai, China

    Bo Yin

  4. Department of Radiation Oncology, Eye and Ent Hospital, Fudan University, Shanghai, China

    Zhu Yi

  5. Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China

    XiuJuan Liu & QingQuan Li

  6. Department of General Surgery, ChangZheng Hospital, Second Military Medical University, Shanghai, China

    ZhiQian Hu & WenChao Gao

  7. Department of Surgery, Jiading Nanxiang Hospital, Shanghai, 201802, China

    HaiWen Yu

Authors
  1. Li Liu
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  2. Bo Yin
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  3. Zhu Yi
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  4. XiuJuan Liu
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  5. ZhiQian Hu
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  7. HaiWen Yu
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  8. QingQuan Li
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Corresponding authors

Correspondence to HaiWen Yu or QingQuan Li.

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Liu, L., Yin, B., Yi, Z. et al. Breast cancer stem cells characterized by CD70 expression preferentially metastasize to the lungs. Breast Cancer 25, 706–716 (2018). https://doi.org/10.1007/s12282-018-0880-6

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  • DOI: https://doi.org/10.1007/s12282-018-0880-6

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