The role of the fibroblast in Barrett's esophagus and esophageal adenocarcinoma.

Abstract

Barrett's esophagus (BE) is the number one risk factor for developing esophageal adenocarcinoma (EAC), a deadly cancer with limited treatment options that has been increasing in incidence in the US. In this report, we discuss current studies on the role of mesenchyme and cancer-associated fibroblasts (CAFs) in BE and EAC, and we highlight translational prospects of targeting these cells. New insights through studies using single-cell RNA sequencing (sc-RNA seq) have revealed an important emerging role of the mesenchyme in developmental signaling and cancer initiation. BE and EAC share similar stromal gene expression, as functional classifications of nonepithelial cells in BE show a remarkable similarity to EAC CAFs. Several recent sc-RNA seq studies and novel organoid fibroblast co-culture systems have characterized the subgroups of fibroblasts in BE and EAC, and have shown that these cells can directly influence the epithelium to induce BE development and cancer progression. Targeting the CAFs in EAC with may be a promising novel therapeutic strategy. The fibroblasts in the surrounding mesenchyme may have a direct role in influencing altered epithelial plasticity during BE development and progression to EAC.