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.
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.
Department of Microbial Chemistry, Kobe Pharmaceutical University, Motoyama-kitamachi, Kobe, Japan. micro-s@kobepharma-u.ac.jp
Yuki
Y
Masuda
Yukihito
Y
Murata
Masahiko
M
Hayashi
Hiroaki
H
Nanba
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005122:Exudates and Transudates / Q000166:cytology; D005260:Female; D005434:Flow Cytometry; D048691:Grifola / Q000737:chemistry*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000187:drug effects*; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D009368:Neoplasm Transplantation; D009929:Organ Size / Q000187:drug effects; D011652:Pulmonary Circulation / Q000187:drug effects*; D013154:Spleen / Q000187:drug effects
D018799:Intercellular Adhesion Molecule-1; D018664:Interleukin-12