Fusobacterium Nucleatum Subspecies Animalis Influences Proinflammatory Cytokine Expression and Monocyte Activation in Human Colorectal Tumors

• Published in: Cancer prevention research (Philadelphia, Pa.) Pa.), 2017-07, Vol.10 (7), p.398-409
• Main Authors: Ye, Xiangcang, Wang, Rui, Bhattacharya, Rajat, Boulbes, Delphine R, Fan, Fan, Xia, Ling, Adoni, Harish, Ajami, Nadim J, Wong, Matthew C, Smith, Daniel P, Petrosino, Joseph F, Venable, Susan, Qiao, Wei, Baladandayuthapani, Veera, Maru, Dipen, Ellis, Lee M
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - immunology; Adenocarcinoma - microbiology; Adenocarcinoma - pathology; Adenocarcinoma - prevention & control; Adult; Aged; Aged, 80 and over; Carcinogenesis - immunology; Cell Line, Tumor; Cell Movement - immunology; Chemokine CCL20 - metabolism; Coculture Techniques; Colorectal Neoplasms - immunology; Colorectal Neoplasms - microbiology; Colorectal Neoplasms - pathology; Colorectal Neoplasms - prevention & control; Disease Progression; Female; Fusobacterium Infections - immunology; Fusobacterium Infections - microbiology; Fusobacterium Infections - pathology; Fusobacterium nucleatum - genetics; Fusobacterium nucleatum - immunology; Fusobacterium nucleatum - isolation & purification; Humans; Interleukin-17 - metabolism; Interleukins - metabolism; Intestinal Mucosa - immunology; Intestinal Mucosa - microbiology; Intestinal Mucosa - pathology; Macrophage Activation - immunology; Male; Middle Aged; Monocytes - immunology; Monocytes - metabolism; Neoplasm Staging; Primary Cell Culture; Real-Time Polymerase Chain Reaction; RNA, Bacterial - genetics; RNA, Ribosomal, 16S - genetics; Sequence Analysis, RNA; Th17 Cells - immunology; Th17 Cells - metabolism; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 1940-6207; 1940-6215
• DOI: 10.1158/1940-6207.CAPR-16-0178

Chronic infection and associated inflammation have long been suspected to promote human carcinogenesis. Recently, certain gut bacteria, including some in the genus, have been implicated in playing a role in human colorectal cancer development. However, the species and subspecies involved and their oncogenic mechanisms remain to be determined. We sought to identify the specific spp. and ssp. in clinical colorectal cancer specimens by targeted sequencing of 16S ribosomal RNA gene. Five spp. were identified in clinical colorectal cancer specimens. Additional analyses confirmed that ssp. was the most prevalent subspecies in human colorectal cancers. We also assessed inflammatory cytokines in colorectal cancer specimens using immunoassays and found that expression of the cytokines IL17A and TNFα was markedly increased but IL21 decreased in the colorectal tumors. Furthermore, the chemokine (C-C motif) ligand 20 was differentially expressed in colorectal tumors at all stages. In co-culture assays, ssp. induced CCL20 protein expression in colorectal cancer cells and monocytes. It also stimulated the monocyte/macrophage activation and migration. Our observations suggested that infection with ssp. in colorectal tissue could induce inflammatory response and promote colorectal cancer development. Further studies are warranted to determine if ssp. could be a novel target for colorectal cancer prevention and treatment. .