TY - JOUR
T1 - Breast cancer colonization by Fusobacterium nucleatum accelerates tumor growth and metastatic progression
AU - Parhi, Lishay
AU - Alon-Maimon, Tamar
AU - Sol, Asaf
AU - Nejman, Deborah
AU - Shhadeh, Amjad
AU - Fainsod-Levi, Tanya
AU - Yajuk, Olga
AU - Isaacson, Batya
AU - Abed, Jawad
AU - Maalouf, Naseem
AU - Nissan, Aviram
AU - Sandbank, Judith
AU - Yehuda-Shnaidman, Einav
AU - Ponath, Falk
AU - Vogel, Jörg
AU - Mandelboim, Ofer
AU - Granot, Zvi
AU - Straussman, Ravid
AU - Bachrach, Gilad
N1 - Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85086841635&partnerID=8YFLogxK
U2 - 10.1038/s41467-020-16967-2
DO - 10.1038/s41467-020-16967-2
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C2 - 32591509
AN - SCOPUS:85086841635
SN - 2041-1723
VL - 11
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 3259
ER -
