IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-020-20733-9.html
   My bibliography  Save this article

Nicotine promotes breast cancer metastasis by stimulating N2 neutrophils and generating pre-metastatic niche in lung

Author

Listed:
  • Abhishek Tyagi

    (Department of Cancer Biology, Wake Forest Baptist Medical Center)

  • Sambad Sharma

    (Department of Cancer Biology, Wake Forest Baptist Medical Center)

  • Kerui Wu

    (Department of Cancer Biology, Wake Forest Baptist Medical Center)

  • Shih-Ying Wu

    (Department of Cancer Biology, Wake Forest Baptist Medical Center)

  • Fei Xing

    (Department of Cancer Biology, Wake Forest Baptist Medical Center)

  • Yin Liu

    (Department of Cancer Biology, Wake Forest Baptist Medical Center)

  • Dan Zhao

    (Department of Cancer Biology, Wake Forest Baptist Medical Center)

  • Ravindra Pramod Deshpande

    (Department of Cancer Biology, Wake Forest Baptist Medical Center)

  • Ralph B. D’Agostino

    (Biostatistics Core, Wake Forest Baptist Medical Center)

  • Kounosuke Watabe

    (Department of Cancer Biology, Wake Forest Baptist Medical Center)

Abstract

Smoking has a profound impact on tumor immunity, and nicotine, which is the major addictive component of smoke, is known to promote tumor progression despite being a non-carcinogen. In this study, we demonstrate that chronic exposure of nicotine plays a critical role in the formation of pre-metastatic niche within the lungs by recruiting pro-tumor N2-neutrophils. This pre-metastatic niche promotes the release of STAT3-activated lipocalin 2 (LCN2), a secretory glycoprotein from the N2-neutrophils, and induces mesenchymal-epithelial transition of tumor cells thereby facilitating colonization and metastatic outgrowth. Elevated levels of serum and urine LCN2 is elevated in early-stage breast cancer patients and cancer-free females with smoking history, suggesting that LCN2 serve as a promising prognostic biomarker for predicting increased risk of metastatic disease in female smoker(s). Moreover, natural compound, salidroside effectively abrogates nicotine-induced neutrophil polarization and consequently reduced lung metastasis of hormone receptor-negative breast cancer cells. Our findings suggest a pro-metastatic role of nicotine-induced N2-neutrophils for cancer cell colonization in the lungs and illuminate the therapeutic use of salidroside to enhance the anti-tumor activity of neutrophils in breast cancer patients.

Suggested Citation

  • Abhishek Tyagi & Sambad Sharma & Kerui Wu & Shih-Ying Wu & Fei Xing & Yin Liu & Dan Zhao & Ravindra Pramod Deshpande & Ralph B. D’Agostino & Kounosuke Watabe, 2021. "Nicotine promotes breast cancer metastasis by stimulating N2 neutrophils and generating pre-metastatic niche in lung," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20733-9
    DOI: 10.1038/s41467-020-20733-9
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-020-20733-9
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-020-20733-9?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Qiaoqi Sui & Xi Zhang & Chao Chen & Jinghua Tang & Jiehai Yu & Weihao Li & Kai Han & Wu Jiang & Leen Liao & Lingheng Kong & Yuan Li & Zhenlin Hou & Chi Zhou & Chenzhi Zhang & Linjie Zhang & Binyi Xiao, 2022. "Inflammation promotes resistance to immune checkpoint inhibitors in high microsatellite instability colorectal cancer," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    2. Jeff Yat-Fai Chung & Philip Chiu-Tsun Tang & Max Kam-Kwan Chan & Vivian Weiwen Xue & Xiao-Ru Huang & Calvin Sze-Hang Ng & Dongmei Zhang & Kam-Tong Leung & Chun-Kwok Wong & Tin-Lap Lee & Eric W-F Lam &, 2023. "Smad3 is essential for polarization of tumor-associated neutrophils in non-small cell lung carcinoma," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20733-9. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.