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具核梭形杆菌是一种主要寄生于口腔的厌氧细菌，是临床最常见的梭形杆菌，近年来被发现常见于人类结直肠癌，并与治疗效果较差相关。小鼠研究发现，进入血液的具核梭形杆菌可以利用其凝集蛋白Fap2与结直肠癌细胞表面的半乳糖-乙酰氨基半乳糖Gal-GalNAc抗原结合，定植于结直肠癌组织。不过，该细菌对于人类乳腺癌的影响尚不明确。 2020年6月26日，英国《自然》旗下《自然通讯》在线发表以色列希伯来大学、魏茨曼科学研究学院、查姆·希巴医疗学中心、马卡比医疗、德国维尔茨堡大学、亥姆霍兹感染研究中心的研究报告，探讨了具核梭形杆菌对人类乳腺癌的影响。 该研究发现，Gal-GalNAc的浓度随着人类乳腺癌的进展而提高，并且乳腺癌标本出现具核梭形杆菌染色体DNA与Gal-GalNAc的高浓度相关。具核梭形杆菌依靠其Fap2与乳腺癌标本的结合可被GalNAc抑制。向血管内注射表达Fap2的具核梭形杆菌能够特异地定植于小鼠乳腺肿瘤，而不表达Fap2的具核梭形杆菌不能定植。注射具核梭形杆菌可以抑制抗肿瘤的T淋巴细胞聚集浸润，并促进肿瘤的生长和转移进程，而能被抗生素治疗逆转。 因此，该研究结果表明，具核梭形杆菌定植于乳腺癌可加速肿瘤的生长和转移进程，乳腺癌治疗期间针对具核梭形杆菌或其Fap2靶点进行干预有望获益。 相关链接 Breast cancer colonization by Fusobacterium nucleatum accelerates tumor growth and metastatic progression. 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 Yehuda-Shnaidman, Falk Ponath, Jorg Vogel, Ofer Mandelboim, Zvi Granot, Ravid Straussman, Gilad Bachrach. Hebrew University-Hadassah School of Dental Medicine, Jerusalem, Israel; Weizmann Institute of Science, Rehovot, Israel; Hebrew University-Hadassah Medical School, Jerusalem, Israel; The Chaim Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel; Maccabi Healthcare Services, Rehovot, Israel; Helmholtz Center for Infection Research, Würzburg, Germany; University of Würzburg, Würzburg, Germany. 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. DOI: 10.1038/s41467-020-16967-2
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