Data from <i>Fusobacterium Nucleatum</i> Subspecies <i>Animalis</i> Influences Proinflammatory Cytokine Expression and Monocyte Activation in Human Colorectal Tumors

Abstract

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