Functional interaction between peritoneal mesothelial cells and stem cells of ovarian yolk sac tumor (SC-OYST) in peritoneal dissemination

Gynecol Oncol. 2012 Feb;124(2):303-10. doi: 10.1016/j.ygyno.2011.10.006. Epub 2011 Oct 29.

Abstract

Objective: In recent years it has been indicated that ecological niches play important roles in the maintenance of cancer stem cells (CSCs). We investigated interactions between peritoneal mesothelial cells and SC-OYST based on the hypothesis that peritoneal mesothelial cells have the potential to provide one of the niches for SC-OYST.

Methods: We divided NOY1 cells into CD133-positive and -negative cells. Using the co-culture of NOY1 and peritoneal mesothelial cells, we compared the expression of CD133, colony formation, and the capacity for migration and invasion. In addition, we assessed the inhibitory effects of AMD3100, a neutralizing antibody against a chemokine receptor (CXCR4). Then, we examined whether AMD3100 affects the tumorigenicity of NOY1-CD133+ cells in vivo.

Results: When NOY1 cells were co-cultured with peritoneal mesothelial cells, we observed the high-level expression of CD133. The number of colonies of NOY1-CD133+ cells was 2.4 times that of NOY1-CD133- cells. In contrast, on co-culture with peritoneal mesothelial cells, it was 4.3 times. When NOY1 cells were cultivated in the upper layer and peritoneal mesothelial cells were cultivated in the lower chamber, NOY1-CD133+ cells showed a greater capacity for migration and invasion than NOY1-CD133- cells. By adding AMD3100 to the co-culture systems, the colony formation, migration, and invasion of NOY1-CD133+ cells were inhibited. In addition, AMD3100 inhibited the tumorigenicity of NOY1-CD133+ cells in vivo.

Conclusions: Our data suggest that peritoneal mesothelial cells have the potential to provide one of the niches for NOY1 cells. Investigation of the niches of SC-OYST will help elucidate important targets for therapeutic approaches.

MeSH terms

  • AC133 Antigen
  • Animals
  • Antigens, CD / biosynthesis
  • Benzylamines
  • Cell Communication / physiology*
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Chemokine CXCL12 / biosynthesis
  • Coculture Techniques
  • Cyclams
  • Endodermal Sinus Tumor / metabolism
  • Endodermal Sinus Tumor / pathology*
  • Epithelium / metabolism
  • Epithelium / pathology*
  • Female
  • Glycoproteins / biosynthesis
  • Heterocyclic Compounds / pharmacology
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Metastasis
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology*
  • Peptides
  • Peritoneal Cavity / pathology*
  • Receptors, CXCR4 / antagonists & inhibitors
  • Receptors, CXCR4 / metabolism

Substances

  • AC133 Antigen
  • Antigens, CD
  • Benzylamines
  • CXCR4 protein, human
  • Chemokine CXCL12
  • Cyclams
  • Glycoproteins
  • Heterocyclic Compounds
  • PROM1 protein, human
  • Peptides
  • Prom1 protein, mouse
  • Receptors, CXCR4
  • plerixafor