Inflammation-Related Carcinogenesis: Lessons from Animal Models to Clinical Aspects.

Futoshi Okada,Mitsuhiko Osaki,Keisuke Goto,Runa Izutsu

doi:10.3390/cancers13040921

Abstract

Simple SummaryIn multicellular organisms, inflammation is the body’s most primitive and essential protective response against any external agent. Inflammation, however, not only causes various modern diseases such as cardiovascular disorders, neurological disorders, autoimmune diseases, metabolic syndrome, infectious diseases, and cancer but also shortens the healthy life expectancy. This review focuses on the onset of carcinogenesis due to chronic inflammation caused by pathogen infections and inhalation/ingestion of foreign substances. This study summarizes animal models associated with inflammation-related carcinogenesis by organ. By determining factors common to inflammatory carcinogenesis models, we examined strategies for the prevention and treatment of inflammatory carcinogenesis in humans.Inflammation-related carcinogenesis has long been known as one of the carcinogenesis patterns in humans. Common carcinogenic factors are inflammation caused by infection with pathogens or the uptake of foreign substances from the environment into the body. Inflammation-related carcinogenesis as a cause for cancer-related death worldwide accounts for approximately 20%, and the incidence varies widely by continent, country, and even region of the country and can be affected by economic status or development. Many novel approaches are currently available concerning the development of animal models to elucidate inflammation-related carcinogenesis. By learning from the oldest to the latest animal models for each organ, we sought to uncover the essential common causes of inflammation-related carcinogenesis. This review confirmed that a common etiology of organ-specific animal models that mimic human inflammation-related carcinogenesis is prolonged exudation of inflammatory cells. Genotoxicity or epigenetic modifications by inflammatory cells resulted in gene mutations or altered gene expression, respectively. Inflammatory cytokines/growth factors released from inflammatory cells promote cell proliferation and repair tissue injury, and inflammation serves as a “carcinogenic niche”, because these fundamental biological events are common to all types of carcinogenesis, not just inflammation-related carcinogenesis. Since clinical strategies are needed to prevent carcinogenesis, we propose the therapeutic apheresis of inflammatory cells as a means of eliminating fundamental cause of inflammation-related carcinogenesis.

Highlights

Inflammation, especially in the chronic form, is the definite cause of tumor development and progression, and it is referred to as “inflammation-related carcinogenesis”
Two categories of scores have been proposed to monitor the systemic inflammatory response, those derived from protein measurement and those based on counting inflammatory cells
C-reactive protein (CRP) is a sensitive and widely used marker of systemic inflammation synthesized by hepatocytes in response to inflammatory cytokines, whose half-life is short because it is catabolized by hepatocytes in 19 hours [173,174]

Summary

Introduction

Inflammation, especially in the chronic form, is the definite cause of tumor development and progression, and it is referred to as “inflammation-related carcinogenesis”. Inflammation is the most effective intrinsic factor required to repeatedly maintain the states of “tissue damage”, “genetic instability”, and “growth stimulation”. Epigenetic alterations such as aberrant DNA hypermethylation are involved in the inflammation-related cancers [2]. From these facts, we understand that inflammation itself promotes genetic alterations (initiator), hyperproliferative response (promoter), and DNA methylation at the same time in the inflammatory sites. We understand that inflammation itself promotes genetic alterations (initiator), hyperproliferative response (promoter), and DNA methylation at the same time in the inflammatory sites All these events from the critical and essential steps for carcinogenesis. The inflammatory environment can generally be understood as the “carcinogenic niche” [3]

Methods

Results

Conclusion