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.

具核梭杆菌是一种口腔厌氧菌，最近发现在人类结直肠癌 (CRC) 中普遍存在，与治疗结果不佳有关。在小鼠中，血源性具核梭菌可以使用其凝集素Fap2定植 CRC 组织，凝集素 Fap2 附着在肿瘤展示的 Gal-GalNAc 上。在这里，我们表明随着人类乳腺癌的进展，Gal-GalNAc 水平会增加，并且乳腺癌样本中F. nucleatum gDNA 的出现与高 Gal-GalNAc 水平相关。我们证明了细菌与乳腺癌样本的 Fap2 依赖性结合，这被 GalNAc 抑制。血管内接种 Fap2 表达F. nucleatumATCC 23726 特异性定植小鼠乳腺肿瘤，而 Fap2 缺陷细菌在肿瘤定植中受损。接种具核梭杆菌可抑制肿瘤浸润性 T 细胞的积累，促进肿瘤生长和转移进展，后两者可通过抗生素治疗来抵消。因此，靶向F. nucleatum或 Fap2 在治疗乳腺癌期间可能是有益的。