Recently, the number of patients with lung cancer has been increasing worldwide. Therapeutic modalities for metastatic lung cancer include surgery, radiotherapy and chemotherapy. Chemotherapy, in particular, is beneficial for preventing further metastasis as it affects not only metastatic lesions but also tumor cells in the blood stream due to the systemic effect of antitumor agents. However, chemotherapy is often associated with serious side effects that lower patients' Quality of Life

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... antly. Subjective side effects include nausea, anorexia, general fatigue and alopecia, while objective side effects such as anemia, thrombocytopenia and leucopenia, which are detectable by laboratory tests, cause immuno-suppression. To attenuate the severity of such events, an immuno-enhancing strategy with concomitant administration of Biological Response Modifer (BRM) agents including lentinan 1) from Lentinus edodes and Protein-bound Polysaccharide K (PSK) 2) from Coriolus versicolor is applied in the 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.