Effects of swainsonine and polyinosinic:polycytidylic acid on murine tumor cell growth and metastasis.
Increased sialylation and branching of asparagine-linked oligosaccharides have recently been associated with both neoplastic transformation and the metastatic phenotype. Swainsonine, an inhibitor of Golgi alpha-mannosidase II blocks the synthesis of sialylated tri- and tetraantennary asparagine-linked oligosaccharides and results in the expression of hybrid-type oligosaccharides at the cell surface. Both the lymphoid tumor line MDAY-D2 and B16F10 melanoma cells were less metastatic when grown in swainsonine (0.3 micrograms/ml) for 48 h prior to injection of the cells into the lateral tail veins of mice. The addition of swainsonine (2.5 micrograms/ml) to the drinking water of the mice further reduced the incidence of lung colonization by B16F10 melanoma cells. MDAY-D2 tumors removed from mice on swainsonine-supplemented drinking water showed a loss of leukoagglutinin-binding complex-type oligosaccharides similar to that of tumor cells cultured in medium containing swainsonine. The growth rate of s.c. MDAY-D2 tumors was not reduced by the addition of swainsonine to the drinking water of the host; however, when mice were given two i.p. injections of the interferon-inducing agent polyinosinic:polycytidylic acid in addition to swainsonine, the primary tumor grew at a reduced rate compared to either treatment alone. Swainsonine alone did not inhibit tumor cell growth in vitro; however, the drug enhanced the antiproliferative effect of interferon. The survival time of mice bearing established MDAY-D2 metastases was extended by treating the animals with swainsonine and polyinosinic:polycytidylic acid; however, the number of long-term survival was unchanged. Swainsonine-treated tumor cells appeared to be compromised in two ways: reduced organ colonization potential; and drug-treated MDAY-D2 cells were more sensitive to the antiproliferative effects of interferon in vitro and in vivo.
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D006023:Glycoproteins / Q000032:analysis; D008361:Mannosidases / Q000037:antagonists & inhibitors*; D051379:Mice; D009362:Neoplasm Metastasis; D009374:Neoplasms, Experimental / Q000032:analysis / Q000188:drug therapy / Q000473:pathology*; D009844:Oligosaccharides / Q000032:analysis; D011070:Poly I-C / Q000494:pharmacology*; D017026:Swainsonine
D000470:Alkaloids; D006023:Glycoproteins; D009844:Oligosaccharides; D008361:Mannosidases; D011070:Poly I-C; D017026:Swainsonine