Analysis of Fusobacterium persistence and antibiotic response in colorectal cancer.

Analysis of Fusobacterium persistence and antibiotic response in colorectal cancer.
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DOI:
10.1126/science.aal5240
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发表时间:
2017-12-15
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Meyerson M
Meyerson M
中科院分区:
其他
文献类型:
--
作者:
Bullman S;Pedamallu CS;Sicinska E;Clancy TE;Zhang X;Cai D;Neuberg D;Huang K;Guevara F;Nelson T;Chipashvili O;Hagan T;Walker M;Ramachandran A;Diosdado B;Serna G;Mulet N;Landolfi S;Ramon Y Cajal S;Fasani R;Aguirre AJ;Ng K;Élez E;Ogino S;Tabernero J;Fuchs CS;Hahn WC;Nuciforo P;Meyerson M

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Colorectal cancers comprise a complex mixture of malignant cells, non-transformed cells, and microorganisms. Fusobacterium nucleatum is among the most prevalent bacterial species in colorectal cancer tissues. Here we show that colonization of human colorectal cancers with Fusobacterium and its associated microbiome, —including Bacteroides, Selenomonas, and Prevotella species, —is maintained in distal metastases, demonstrating microbiome stability between paired primary and -metastatic tumors. In situ hybridization analysis revealed that Fusobacterium is predominantly associated with cancer cells in the metastatic lesions. Mouse xenografts of human primary colorectal adenocarcinomas were found to retain viable Fusobacterium and its associated microbiome through successive passages. Treatment of mice bearing a colon cancer xenograft with the antibiotic metronidazole reduced Fusobacterium load, cancer cell proliferation, and overall tumor growth. These observations argue for further investigation of antimicrobial interventions as a potential treatment for patients with Fusobacterium-associated colorectal cancer.
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