Analysis of Fusobacterium persistence and antibiotic response in colorectal cancer

被引：1218

作者：

Bullman, Susan ^{[1
,2
]}

Pedamallu, Chandra S. ^{[1
,2
]}

Sicinska, Ewa ^{[1
]}

Claney, Thomas E. ^{[3
]}

Zhang, Xiaoyang ^{[1
,2
]}

Cai, Diana ^{[1
,2
]}

Neuberg, Donna ^{[1
]}

Huang, Katherine ^{[2
]}

Guevara, Fatima ^{[1
]}

Nelson, Timothy ^{[1
]}

Chipashvili, Otari ^{[1
]}

Hagan, Timothy ^{[1
]}

Walker, Mark ^{[2
]}

Ramachandran, Aruna ^{[1
,2
]}

Diosdado, Begona ^{[1
,2
]}

Serna, Garazi ^{[4
]}

Mulet, Nuria ^{[4
]}

Landolfi, Stefania ^{[4
]}

Ramon y Cajal, Santiago ^{[4
]}

Fasani, Roberta ^{[4
]}

Aguirre, Andrew J. ^{[1
,2
,3
]}

Ng, Kimmie ^{[1
]}

Elez, Elena ^{[4
]}

Ogino, Shuji ^{[1
,3
,5
]}

Tabernero, Josep ^{[4
]}

Fuchs, Charles S. ^{[6
]}

Hahn, William C. ^{[1
,2
,3
]}

Nuciforo, Paolo ^{[4
]}

Meyerson, Matthew ^{[1
,2
,3
]}

机构：

[1] Harvard Med Sch, Dana Farber Canc Inst, Boston, MA 02115 USA

[2] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

[3] Harvard Med Sch, Brigham & Womens Hosp, Boston, MA 02115 USA

[4] Univ Autonoma Barcelona, Vall dHebron Univ Hosp, Vall dHebron Inst Oncol, CIBERONC, Barcelona, Spain

[5] Harvard TH Chan Sch Publ Hlth, Boston, MA 02115 USA

[6] Yale Sch Med, Yale Canc Ctr, New Haven, CT 06520 USA

来源：

SCIENCE | 2017年 / 358卷 / 6369期

关键词：

MOLECULAR-FEATURES; NUCLEATUM; COLON; TUMORIGENESIS; CARCINOGENESIS; INFLAMMATION; ASSOCIATION; MICROBIOTA; BINDING; CELLS;

D O I：

10.1126/science.aal5240

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Colorectal cancers comprise a complex mixture of malignant cells, nontransformed 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.

引用

页码：1443 / +

页数：6

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