Inhibitory effect of MD-Fraction on tumor metastasis: involvement of NK cell activation and suppression of intercellular adhesion molecule (ICAM)-1 expression in lung vascular endothelial cells

Biol Pharm Bull. 2008 Jun;31(6):1104-8. doi: 10.1248/bpb.31.1104.

Abstract

The anti-metastatic activity of MD-Fraction extracted from the maitake mushroom (Grifola frondosa) was examined in an experimental murine model of lung metastasis. Intraperitoneal administration of MD-Fraction 2 d before tumor implantation significantly inhibited lung metastasis of colon-26 carcinoma and B16/BL6 melanoma cells. In this model, MD-Fraction enhanced IL-12 production from antigen presenting cells (APCs). MD-Fraction treatment activated NK cells and increased cytotoxicity against YAC-1 and colon-26 carcinoma cells. Furthermore, the depletion of NK cells with anti-asialo GM1 abolished the inhibitory effect of MD-Fraction on lung metastasis of colon-26 cells. Ex vivo, B16/BL6 cell adhesion to LPS-activated murine lung vascular endothelial cells was inhibited by MD-Fraction and anti-intercellular adhesion molecule (ICAM)-1 antibody. These results suggest that MD-Fraction inhibits tumor metastasis by activating NK cells and APCs, and by suppressing of ICAM-1 leading to the inhibition of tumor cell adhesion to vascular endothelial cells.

MeSH terms

  • Animals
  • Cell Survival / drug effects
  • Colonic Neoplasms / pathology
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism*
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism*
  • Exudates and Transudates / cytology
  • Female
  • Flow Cytometry
  • Grifola / chemistry*
  • Intercellular Adhesion Molecule-1 / biosynthesis*
  • Interleukin-12 / biosynthesis
  • Killer Cells, Natural / drug effects*
  • Lung Neoplasms / prevention & control
  • Lung Neoplasms / secondary
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Metastasis / prevention & control*
  • Neoplasm Transplantation
  • Organ Size / drug effects
  • Pulmonary Circulation / drug effects*
  • Spleen / drug effects

Substances

  • Intercellular Adhesion Molecule-1
  • Interleukin-12