PGE2-associated inflammation and gastrointestinal tumorigenesis

Abstract

Accumulating evidence has indicated that chronic inflammation is associated with a variety of diseases, including cancer, heart attacks, Alzheimer’s and other diseases. In the cancer research field, the association of inflammatory infiltration with cancer has been known histologically for a long time. Recent studies have indicated that macrophages and other immune cells infiltrate cancer tissues, expressing cytokines, chemokines and growth factors, thereby constructing an inflammatory microenvironment. In such a microenvironment, nuclear factor (NF)-κB is activated, which contributes to the growth and survival of cancer cells. Moreover, it has also been shown that NF-κB activation is associated with the acquisition of stem cell properties by cancer cells. Using inflammation-associated gastric cancer model mice (Gan mice), we have shown that tumor necrosis factor (TNF)-α signaling is activated in the inflammatory microenvironment and plays a tumor-promoting role by inducing Noxo1 in tumor cells. Taken together, these results indicate that regulation of chronic inflammation in tumor tissues would be an effective preventive and/or therapeutic strategy against cancer development and malignant progression.