Role of Microbial Infection-Induced Inflammation in the Development of Gastrointestinal Cancers

Abstract

There has been increasing evidence that a local inflammatory response stimulates tumor cells to acquire metastatic potential, and the concept of inflammatory oncotaxis has been spreading in recent years. However, the interaction between microbial inflammation and the development of gastrointestinal cancer is still unclear. This review summarizes the present knowledge on the role of microbial inflammation in the development of gastrointestinal cancers from the perspective of molecular biological findings. Chronic inflammation caused by bacterial infection is known to induce cancers as exemplified by Helicobacter pylori, which is associated with the development of gastric cancer via the activation of the TLR4 pathway by bacterial lipopolysaccharide followed by cancer growth through CagA-MET signaling. In addition, the development of inflammatory bowel diseases has been known to become a risk factor for colorectal cancers, where inflammation caused by certain bacterial infections plays a key role. It is also known that the cancer microenvironment is associated with cancer growth. Moreover, infectious complication after surgery for gastrointestinal cancers may promote tumor progression via the stimulation of pathogen-associated molecular patterns and various inflammatory mediators secreted by immunocytes. Further research on the link between microbial inflammation and cancer progression is needed to drive a paradigm shift in cancer treatment.

Keywords: gastrointestinal cancer; microbial inflammation; tumor progression.

Figure 1

An overview of the links between microbial infection, chronic inflammation, and cancer environment. Several signaling pathways, such as TLR4 and CagA/c-Met, and mediators selected by microbial inflammation play an important role in the development of gastrointestinal cancers. EBV: Epstein-Barr virus; CAFs: Cancer associated fibroblasts; EMT: Epithelial mesenchymal transition; HGF: Hepatocyte growth factor; HPV: Human papilloma virus; IFN: Interferon; ILs: Interleukins; ICAM-1: Intercellular adhesion molecule-1; JAK/STAT1: Janus kinase/Signal transducer and activator of transcription 1; LPS: Lipopolysaccharide, MMPs: Matrix metalloproteinases; NF-κβ: nuclear factor-kappa β; PAMPs: Pathogen-associated molecular pattern molecules; RANTES: Regulated on activation, normal T cell expressed and secreted; TAMs: Tumor associated macrophages; TGFs: Transforming growth factor; TLR: Toll-like receptor; TNF-α: Tumor necrosis factor-α; VCAM-1: Vascular cell adhesion molecule-1.