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

Abstract

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..

Nomogram for predicting overall survival in stage II‐III colorectal cancer

“…28 One study showed that systemic chemotherapy and regional chemotherapy reduced hematogenous metastasis in patients with CRC after resection, suggesting improved survival rates. 29 Therefore, the inclusion of these four clinical features into our nomogram is consistent with the findings of these previous works.…”

“…That signified that PDW was an advantageous prognostic factor for the survival of patients with CRC. Furthermore, research has suggested that colorectal infection could induce an inflammatory reaction and promote CRC development . Therefore, we speculated that monocytes, which play an essential role in the inflammatory response, could be an independent prognostic factor.…”

“…Furthermore, research has suggested that colorectal infection could induce an inflammatory reaction and promote CRC development. 29 Therefore, we speculated that monocytes, which play an essential role in the inflammatory response, could be an independent prognostic factor. As independent prognostic factors, MPV, PDW, and monocytes are easily collected from routine blood tests.…”

Role of human microbiota in the development of colorectal cancer

“…Fusobacterium nucleatum являются анаэробными грамположительными комменсалами и связаны с периодонтитом, неблагоприятными исходами беременности, сердечно-сосудистыми заболеваниями, ревматоидным артритом, воспалительными заболеваниями кишечника и КРР [54]. При сравнении тканей КРР с подобранными нормальными тканями было обнаружено, что Fusobacterium nucleatum преобладают в тканях тубулярных аденом и рака толстой кишки [28,44,[55][56][57]. Имеются данные о том, что присутствие Fusobacterium в тканях КРР свидетельствует о худшем прогнозе заболевания у пациентов [43,58].…”

“…Имеются данные о том, что присутствие Fusobacterium в тканях КРР свидетельствует о худшем прогнозе заболевания у пациентов [43,58]. Наличие Fusobacterium при КРР также коррелирует с повышенной экспрессией IL-17A и TNF-α, которые способствуют канцерогенезу [55]. FadA-адгезиновый белок из Fusobacterium nucleatum избирательно связывается с E-кадгерином и активирует передачу сигналов β-catenin в эпителиальных клетках толстой кишки [59].…”