Journal Article

Analysis of Fusobacterium persistence and antibiotic response in colorectal cancer

Huang, Katherine, Neuberg, Donna, Walker, Mark, Ramachandran, Aruna, Élez, Elena, Tabernero, Josep, Pedamallu, Chandra S., Cai, Diana, Nuciforo, Paolo, Chipashvili, Otari, Ogino, Shuji, Guevara, Fatima, Zhang, Xiaoyang, Fasani, Roberta, Ramon y Cajal, Santiago, Ng, Kimmie, Nelson, Timothy, Aguirre, Andrew J., Bullman, Susan, Diosdado, Begoña, Serna, Garazi, Hahn, William C., Meyerson, Matthew, Fuchs, Charles S., Hagan, Timothy, Sicinska, Ewa, Clancy, Thomas E., Mulet, Nuria, Landolfi, Stefania

2017

Overview

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.

• Publisher: American Association for the Advancement of Science,The American Association for the Advancement of Science
• Subject: Adenocarcinoma - drug therapy / Adenocarcinoma - microbiology / Adenocarcinoma - secondary / Animals / Anti-Bacterial Agents - pharmacology / Anti-Bacterial Agents - therapeutic use / Antibiotics / Bacteria / Bacteroides - drug effects / Cancer / Carcinogenesis / Cell proliferation / Colon / Colon cancer / Colonization / Colorectal cancer / Colorectal Neoplasms - drug therapy / Colorectal Neoplasms - microbiology / Colorectal Neoplasms - pathology / Fusobacterium / Fusobacterium - drug effects / Fusobacterium - genetics / Fusobacterium - isolation & purification / Fusobacterium nucleatum / Health risk assessment / HT29 Cells / Humans / Hybridization analysis / Lesions / Liver Neoplasms - microbiology / Liver Neoplasms - secondary / Metastases / Metastasis / Metronidazole / Metronidazole - pharmacology / Metronidazole - therapeutic use / Mice / Microbiomes / Microbiota - drug effects / Microorganisms / Prevotella - drug effects / Species / Stability analysis / Stroma / Therapeutic applications / Tumorigenesis / Tumors / Xenograft Model Antitumor Assays / Xenografts