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

Nat Commun. 2020 Jun 26;11(1):3259. doi: 10.1038/s41467-020-16967-2.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Bacterial Proteins / metabolism
  • Breast Neoplasms / diagnostic imaging
  • Breast Neoplasms / immunology
  • Breast Neoplasms / microbiology*
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Colony Count, Microbial
  • DNA, Bacterial / genetics
  • Disease Models, Animal
  • Disease Progression*
  • Female
  • Fusobacterium nucleatum / drug effects
  • Fusobacterium nucleatum / genetics
  • Fusobacterium nucleatum / growth & development*
  • Galactosamine / metabolism
  • Galactose / metabolism
  • Genome, Bacterial / genetics
  • Humans
  • Immunity / drug effects
  • Lung Neoplasms / secondary
  • Mice, Inbred BALB C
  • Neoplasm Metastasis

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • DNA, Bacterial
  • Galactosamine
  • Galactose