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Breast cancer colonization by Fusobacterium nucleatum accelerates tumor growth and metastatic progression

Author

Listed:
  • Lishay Parhi

    (The Hebrew University-Hadassah School of Dental Medicine)

  • Tamar Alon-Maimon

    (The Hebrew University-Hadassah School of Dental Medicine)

  • Asaf Sol

    (The Hebrew University-Hadassah School of Dental Medicine)

  • Deborah Nejman

    (Weizmann Institute of Science)

  • Amjad Shhadeh

    (The Hebrew University-Hadassah School of Dental Medicine)

  • Tanya Fainsod-Levi

    (Hebrew University-Hadassah Medical School)

  • Olga Yajuk

    (Hebrew University-Hadassah Medical School)

  • Batya Isaacson

    (Hebrew University-Hadassah Medical School)

  • Jawad Abed

    (The Hebrew University-Hadassah School of Dental Medicine)

  • Naseem Maalouf

    (The Hebrew University-Hadassah School of Dental Medicine)

  • Aviram Nissan

    (The Chaim Sheba Medical Center, Tel Hashomer)

  • Judith Sandbank

    (The Pathology Institute, Maccabi Healthcare Services)

  • Einav Yehuda-Shnaidman

    (The Pathology Institute, Maccabi Healthcare Services)

  • Falk Ponath

    (Helmholtz Institute for RNA-based Infection Research (HIRI), Helmholtz Center for Infection Research (HZI))

  • Jörg Vogel

    (Helmholtz Institute for RNA-based Infection Research (HIRI), Helmholtz Center for Infection Research (HZI)
    University of Würzburg)

  • Ofer Mandelboim

    (Hebrew University-Hadassah Medical School)

  • Zvi Granot

    (Hebrew University-Hadassah Medical School)

  • Ravid Straussman

    (Weizmann Institute of Science)

  • Gilad Bachrach

    (The Hebrew University-Hadassah School of Dental Medicine)

Abstract

Fusobacterium nucleatum is an oral anaerobe recently found to be prevalent in human colorectal cancer (CRC) where it is associated with poor treatment outcome. In mice, hematogenous F. nucleatum can colonize CRC tissue using its lectin Fap2, which attaches to tumor-displayed Gal-GalNAc. Here, we show that Gal-GalNAc levels increase as human breast cancer progresses, and that occurrence of F. nucleatum gDNA in breast cancer samples correlates with high Gal-GalNAc levels. We demonstrate Fap2-dependent binding of the bacterium to breast cancer samples, which is inhibited by GalNAc. Intravascularly inoculated Fap2-expressing F. nucleatum ATCC 23726 specifically colonize mice mammary tumors, whereas Fap2-deficient bacteria are impaired in tumor colonization. Inoculation with F. nucleatum suppresses accumulation of tumor infiltrating T cells and promotes tumor growth and metastatic progression, the latter two of which can be counteracted by antibiotic treatment. Thus, targeting F. nucleatum or Fap2 might be beneficial during treatment of breast cancer.

Suggested Citation

  • Lishay Parhi & Tamar Alon-Maimon & Asaf Sol & Deborah Nejman & Amjad Shhadeh & Tanya Fainsod-Levi & Olga Yajuk & Batya Isaacson & Jawad Abed & Naseem Maalouf & Aviram Nissan & Judith Sandbank & Einav , 2020. "Breast cancer colonization by Fusobacterium nucleatum accelerates tumor growth and metastatic progression," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16967-2
    DOI: 10.1038/s41467-020-16967-2
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    Cited by:

    1. Meghana Pagadala & Timothy J. Sears & Victoria H. Wu & Eva Pérez-Guijarro & Hyo Kim & Andrea Castro & James V. Talwar & Cristian Gonzalez-Colin & Steven Cao & Benjamin J. Schmiedel & Shervin Goudarzi , 2023. "Germline modifiers of the tumor immune microenvironment implicate drivers of cancer risk and immunotherapy response," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    2. Julia D. Ransohoff & Victor Ritter & Natasha Purington & Karen Andrade & Summer Han & Mina Liu & Su-Ying Liang & Esther M. John & Scarlett L. Gomez & Melinda L. Telli & Lidia Schapira & Haruka Itakura, 2023. "Antimicrobial exposure is associated with decreased survival in triple-negative breast cancer," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    3. João Botelho & Paulo Mascarenhas & João Viana & Luís Proença & Marco Orlandi & Yago Leira & Leandro Chambrone & José João Mendes & Vanessa Machado, 2022. "An umbrella review of the evidence linking oral health and systemic noncommunicable diseases," Nature Communications, Nature, vol. 13(1), pages 1-11, December.

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