# Extracellular Adenosine in Gastric Cancer: The Role of GCSCs

## TL;DR

This study explores how gastric cancer stem cells produce and manage adenosine, suggesting new ways to target these cells for treatment.

## Contribution

The study reveals unique adenosine metabolism features in gastric cancer stem cells, highlighting potential therapeutic targets.

## Key findings

- GCSCs release more ATP and express higher CD39, enhancing ATP hydrolysis.
- GCSCs efficiently hydrolyze AMP via CD73 despite stable CD73 levels.
- GCSCs show increased ENT2 protein expression, affecting adenosine transport.

## Abstract

Gastric cancer (GC) is among the most common and deadliest types of cancer, with a poor prognosis primarily due to late-stage detection and the presence of cancer stem cells (CSCs). This study investigates the mechanisms regulating extracellular adenosine levels in gastric cancer stem-like cells (GCSCs) derived from the MKN-74 cell line. Our results show that GCSCs release more ATP into the extracellular medium and exhibit higher levels of CD39 expression, which enables them to hydrolyze a greater amount of ATP. Furthermore, we also found that GCSCs possess a greater capacity to hydrolyze AMP, primarily due to the activity of the CD73 protein, with no significant changes in CD73 transcripts and protein levels between GCSCs and differentiated cells. Additionally, adenosine transport is primarily mediated by members of the equilibrative nucleoside transporter (ENT) family in GCSCs, where a significant increase in the expression level of the ENT2 protein is observed compared to non-GCSCs MKN-74 cells. These findings suggest that targeting the adenosine metabolism pathway in GCSCs could be a potential therapeutic strategy for gastric cancer.