Lgr5-Positive Cells are Cancer-Stem-Cell-Like Cells in Gastric Cancer

BACKGROUND/AIMS: Effective treatment of gastric cancer (GC) requires better understanding of the molecular regulation of its carcinogenesis. Identification of cancer stem cells (CSCs) in GC appears to be a critical question. METHODS: We analyzed Lgr5 expression in GC specimen. We used an adeno-associated virus (AAV) that carries diphtheria toxin fragment A (DTA) under the control of Lgr5 promoter (AAV-pLgr5-DTA) to transduce human GC cells. The growth of GC cells with/without depletion of Lgr5-positive cells was studied in vitro in an MTT assay, and in vivo by analyzing bioluminescence levels. RESULTS: A portion of GC cells in the resected specimen expressed Lgr5. GC cells that formed tumor spheres expressed high Lgr5. Selective depletion of Lgr5-positive GC cells resulted in significant growth inhibition of GC cells in vitro and in vivo. CONCLUSION: Lgr5-positive cells may be CSCs-like cells in GC and may play a pivotal role in the tumorigenesis of GC. Treating Lgr5-positive GC cells may substantially improve the therapeutic outcome.