Macrophages activate mesenchymal stem cells to acquire cancer-associated fibroblast-like features resulting in gastric epithelial cell lesions and malignant transformation in vitro

Abstract

The majority of premalignant gastric lesions develop in the mucosa that has been modified by chronic inflammation. As components of the gastritis microenvironment, mesenchymal stem cells (MSCs) and macrophages are critically involved in the initiation and development of the chronic gastritis-associated gastric epithelial lesions/malignancy process. However, in this process, the underlying mechanism of macrophages interacting with MSCs, particularly the effect of macrophages on MSCs phenotype and function remains to be elucidated. The present study revealed that human umbilical cord-derived MSCs were induced to differentiate into cancer-associated fibroblasts (CAFs) phenotype by co-culture with macrophages (THP-1 cells) in vitro, and which resulted in gastric epithelial lesions/potential malignancy via epithelial-mesenchymal transition-like changes. The results of the present study indicated that macrophages could induce MSCs to acquire CAF-like features and a pro-inflammatory phenotype to remodel the inflammatory microenvironment, which could potentiate oncogenic transformation of gastric epithelium cells. The present study provides potential targets and options for inflammation-associated gastric cancer prevention and intervention.