Format

Send to

Choose Destination
Cancer Prev Res (Phila). 2017 Jul;10(7):398-409. doi: 10.1158/1940-6207.CAPR-16-0178. Epub 2017 May 8.

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

Author information

1
Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. lellis@mdanderson.org xcye@mdanderson.org.
2
Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
3
Alkek Center for Metagenomics and Microbiome Research, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas.
4
Texas Children's Microbiome Center, Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas.
5
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
6
Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
7
Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Abstract

Chronic infection and associated inflammation have long been suspected to promote human carcinogenesis. Recently, certain gut bacteria, including some in the Fusobacterium genus, have been implicated in playing a role in human colorectal cancer development. However, the Fusobacterium species and subspecies involved and their oncogenic mechanisms remain to be determined. We sought to identify the specific Fusobacterium spp. and ssp. in clinical colorectal cancer specimens by targeted sequencing of Fusobacterium 16S ribosomal RNA gene. Five Fusobacterium spp. were identified in clinical colorectal cancer specimens. Additional analyses confirmed that Fusobacterium nucleatum ssp. animalis was the most prevalent F. nucleatum 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 in vitro co-culture assays, F. nucleatum ssp. animalis 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 F. nucleatum ssp. animalis in colorectal tissue could induce inflammatory response and promote colorectal cancer development. Further studies are warranted to determine if F. nucleatum ssp. animalis could be a novel target for colorectal cancer prevention and treatment. Cancer Prev Res; 10(7); 398-409. ©2017 AACR.

PMID:
28483840
DOI:
10.1158/1940-6207.CAPR-16-0178
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center