Stem cells in gastric cancer.

Gastric cancer (GC) is one of the leading causes of cancer-related mortality worldwide. Cancer stem cells (CSCs), which were first identified in acute myeloid leukemia and subsequently in a large array of solid tumors, play important roles in cancer initiation, dissemination and recurrence. CSCs are often transformed tissue-specific stem cells or de-differentiated transit amplifying progenitor cells. Several populations of multipotent gastric stem cells (GSCs) that reside in the stomach have been determined to regulate physiological tissue renewal and injury repair. These populations include the Villin+ and Lgr5+ GSCs in the antrum, the Troy+ chief cells in the corpus, and the Sox2+ GSCs that are found in both the antrum and the corpus. The disruption of tumor suppressors in Villin+ or Lgr5+ GSCs leads to GC in mouse models. In addition to residing GSCs, bone marrow-derived cells can initiate GC in a mouse model of chronic Helicobacter infection. Furthermore, expression of the cell surface markers CD133 or CD44 defines gastric CSCs in mouse models and in human primary GC tissues and cell lines. Targeted elimination of CSCs effectively reduces tumor size and grade in mouse models. In summary, the recent identification of normal GSCs and gastric CSCs has greatly improved our understanding of the molecular and cellular etiology of GC and will aid in the development of effective therapies to treat patients.