Identification and expansion of cancer stem cells in tumor tissues and peripheral blood derived from gastric adenocarcinoma patients

Cell Res. 2012 Jan;22(1):248-58. doi: 10.1038/cr.2011.109. Epub 2011 Jul 5.

Abstract

Gastric cancer is the fourth most common cancer worldwide, with a high rate of death and low 5-year survival rate. To date, there is a lack of efficient therapeutic protocols for gastric cancer. Recent studies suggest that cancer stem cells (CSCs) are responsible for tumor initiation, invasion, metastasis, and resistance to anticancer therapies. Thus, therapies that target gastric CSCs are attractive. However, CSCs in human gastric adenocarcinoma (GAC) have not been described. Here, we identify CSCs in tumor tissues and peripheral blood from GAC patients. CSCs of human GAC (GCSCs) that are isolated from tumor tissues and peripheral blood of patients carried CD44 and CD54 surface markers, generated tumors that highly resemble the original human tumors when injected into immunodeficient mice, differentiated into gastric epithelial cells in vitro, and self-renewed in vivo and in vitro. Our findings suggest that effective therapeutic protocols must target GCSCs. The capture of GCSCs from the circulation of GAC patients also shows great potential for identification of a critical cell population potentially responsible for tumor metastasis, and provides an effective protocol for early diagnosis and longitudinal monitoring of gastric cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / blood*
  • Adenocarcinoma / pathology
  • Animals
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / metabolism
  • Cell Transformation, Neoplastic / metabolism
  • Epithelial Cells / cytology
  • Humans
  • Hyaluronan Receptors / metabolism
  • Intercellular Adhesion Molecule-1 / metabolism
  • Mice
  • Mice, SCID
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology*
  • Neoplastic Stem Cells / transplantation
  • Stomach Neoplasms / blood*
  • Stomach Neoplasms / pathology
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers, Tumor
  • CD44 protein, human
  • Hyaluronan Receptors
  • Intercellular Adhesion Molecule-1