Antitumor activity of alpha-galactosylceramide, KRN7000, in mice with the melanoma B16 hepatic metastasis and immunohistological study of tumor infiltrating cells.

Abstract

Liver metastasis of primary tumors is clinically a major problem. We examined the antitumor activity of KRN7000, an alpha-galactosylceramide, in mice with liver metastasis of the B16 melanoma. KRN7000 significantly inhibited tumor growth in the liver, and its potency was similar to that of interleukin-12. The KRN7000 administration resulted in a high percentage of cured mice, which acquired tumor-specific immunity. To study what kinds of antitumor effector cells participated in killing tumor cells, we then performed immunohistological analysis of tumor-infiltrating cells, and found that KRN7000 induced marked invasion of NK1.1+ cells, CD8+ cells, and F4/80+ cells (macrophages) into B16 tumor nodules. In addition, it appeared that KRN7000-treated, liver-associated macrophages possessed strong lytic activity against tumor cells. These results suggest that NK cells, NK1.1+ T (NKT) cells, cytotoxic T lymphocytes, and macrophages play an important role in killing tumor cells in the liver, and that KRN7000 may be useful for the treatment of cancer liver metastasis.

• Authors: R Nakagawa, I Serizawa, K Motoki, M Sato, H Ueno, R Iijima, H Nakamura, A Shimosaka, Y Koezuka
• Journal: Oncology research (Oncol Res) Vol. 12 Issue 2 Pg. 51-8 ( 2000) ISSN: 0965-0407 [Print] United States
• PMID: 11132924 (Publication Type: Journal Article)

Chemical References

• Antigens
• Antigens, Differentiation
• Antigens, Ly
• Antigens, Surface
• Antineoplastic Agents
• CD8 Antigens
• Galactosylceramides
• Klrb1c protein, mouse
• Lectins, C-Type
• NK Cell Lectin-Like Receptor Subfamily B
• Proteins
• Recombinant Proteins
• monocyte-macrophage differentiation antigen
• Interleukin-12
• KRN 7000

Topics

• Animals
• Antigens (metabolism)
• Antigens, Differentiation (metabolism)
• Antigens, Ly
• Antigens, Surface
• Antineoplastic Agents (pharmacology, therapeutic use)
• CD8 Antigens (metabolism)
• Female
• Galactosylceramides (pharmacology, therapeutic use)
• Immunohistochemistry
• Interleukin-12 (pharmacology)
• Lectins, C-Type
• Liver Neoplasms (secondary)
• Macrophages (metabolism)
• Melanoma, Experimental (drug therapy, pathology)
• Mice
• Mice, Inbred C57BL
• NK Cell Lectin-Like Receptor Subfamily B
• Neoplasm Metastasis
• Neoplasm Transplantation
• Proteins (metabolism)
• Recombinant Proteins (pharmacology)
• Time Factors
• Tumor Cells, Cultured