Analysis of Fusobacterium persistence and antibiotic response in colorectal cancer
Susan Bullman1,2, Chandra S. Pedamallu1,2, Ewa Sicinska1, Thomas E. Clancy3, Xiaoyang Zhang1,2, Diana Cai1,2, Donna Neuberg1, Katherine Huang2, Fatima Guevara1, Timothy Nelson1, Otari Chipashvili1, Timothy Hagan1, Mark Walker2, Aruna Ramachandran1,2, Begoña Diosdado1,2, Garazi Serna4, Nuria Mulet4, Stefania Landolfi4, Santiago Ramon y Cajal4, Roberta Fasani4, Andrew J. Aguirre1,2,3, Kimmie Ng1, Elena Élez4, Shuji Ogino1,3,5, Josep Tabernero4, Charles S. Fuchs6, William C. Hahn1,2,3, Paolo Nuciforo4, Matthew Meyerson1,2,3,*
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Science 23 Nov 2017:
eaal5240
DOI: 10.1126/science.aal5240
Abstract
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-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.
1
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
2
Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
3
Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
4
Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, CIBERONC, Universitat Autònoma de Barcelona, Spain.
5
Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
6
Yale Cancer Center, Yale School of Medicine, New Haven, CT, USA.
7
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA. matthew_meyerson@dfci.harvard.edu.
大腸がんが感染症だとしたら、疫病としてみたときその拡大は米国中南部の畜産酪農における抗生物質投与と肥満の相関と同様に気になる。
