The regulation of stem-like property in gastric cancer cells mediated by tumor associated macrophage.

Abstract

e13553 Background: CD44 has recently been identified as one of the cell surface markers associated with cancer stem cells (CSCs) in several types of tumor. We have reported the functional role of CD44 variant isoform in the maintenance of low reactive oxygen species (ROS) levels in gastrointestinal cancer cells. Previous studies demonstrated that tumor associated macrophage promotes tumor progression, but the functional role for macrophage in the regulation of CSC marker expression is not known. Methods: We analysed the relationship of CSCs and macrophage infiltration in gastric cancer cell lines and human gastric cancer samples. Results: Here, we showed activated macrophage by LPS and IFNγ produces inflammatory cytokines and chemokines, and these macrophage express CD68 and CD163, which are known as specific markers for pan-macrophage and M2 macrophage. we found that co-culture with activated macrophage triggers the CD44 and Bmi1 expression in gastric cancer cells and promote stem-like property that possess sphere-forming ability. Furthermore, we investigated the relation between CD44 expression and infiltrated macrophage in human gastric cancer. The staining patterns of CD44, Bmi1 and macrophage specific markers (CD68 and CD163) were significantly correlated in tumorous tissues of human gastric adenocarcinoma. Conclusions: These findings establish inflammatory cytokines, which producted from activated macrophage, induce the CD44 and Bmi1 expression in gastric cancer cells. These findings revealed that a role for tumor associated macrophage in the expansion of gastric cancer stem-like cells and subsequent malignant progression.