The Significance of Arginase I Administration on the Survival of Mice Bearing NS-1 Myeloma Cells

BackgroundArginase I blood levels elevate in cancerous patients and correlate with cancer stages and poor prognosis. Since arginase is capable of enhancing cell growth, it is unclear whether its ominous effect on cancer progression is through the inhibition of immunity or through direct enhancement of cancer cell growth. We tried to clarify this question.MethodsNS-1 mouse myeloma cells were inoculated intraperitoneally (i.p.) into mice. Purified mouse arginase I was injected daily either intravenously (i.v.) or i.p. for 6 d. A tumor-only control group received i.p. tumor cells without arginase. The survival rates of all mice were recorded.ResultsSurvival rates were significantly lower in the i.v. group than in the i.p. group (P=0.017) or in the tumor-only control group (P=0.034). As spleen is readily exposed to i.v. arginase, its natural killer cells were studied and were found to have been significantly suppressed by arginase in vitro (P<0.005).ConclusionOur results indicate that the direct inhibition of the immune system by i.v. arginase is more significant in shortening the survival of tumor-bearing mice than localized (i.p.) arginase promotion of tumor cell growth. Thus, an elevation of arginase in a patient's blood is very harmful to the host immune system, e.g. splenic natural killer cells.