fr-167653 and Neoplasm-Metastasis

Carcinoembryonic antigen (CEA) has been reported to promote the metastatic potential in some experimental tumors. Adhesion molecules are known to play an important role in the process of metastasis. Cytokines, including interleukin 1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), which are produced by Kupffer cells, induce endothelial cells to express adhesion molecules. As a result, the present study was designed to investigate whether the interaction between CEA and Kupffer cells accelerated the metastatic potential of tumors in the liver. Kupffer cells isolated from the liver of male BALB/c mice were cultured with CEA, either with or without the addition of a cytokine inhibitor. The levels of IL-1beta and TNF-alpha were examined in a culture medium. An adhesion assay of colon cancer cell lines to human umbilical vein endothelial cells was also performed. When CEA was added to the Kupffer cell culture medium, cytokines were produced. Elevated levels of cytokines appeared to lead to increased rates of adhesion of cancer cells to endothelial cells. However, these phenomena were blocked by the addition of cytokine inhibitors. CEA stimulated Kupffer cells to produce cytokines. An elevated number of cytokines have been proven to promote the expression of adhesion molecules in endothelial cells. These processes are therefore considered to contribute to the metastasis of malignant cells to the liver. These results suggest that cytokine inhibitors may therefore play an important role in the inhibition of hepatic metastasis.

Topics: Animals; Antigens, Tumor-Associated, Carbohydrate; CA-19-9 Antigen; Carcinoembryonic Antigen; Cell Adhesion; Cell Communication; Colonic Neoplasms; Culture Media; Disease Progression; Dose-Response Relationship, Drug; E-Selectin; Endothelium, Vascular; Gangliosides; Humans; Interleukin-1; Kupffer Cells; Male; Mice; Mice, Inbred BALB C; Neoplasm Metastasis; Oligosaccharides; Pyrazoles; Pyridines; Sialyl Lewis X Antigen; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha