Possible role of immune surveillance at the initial phase of metastasis produced by B16BL6 melanoma cells

The relationship among the real-time trafficking of lung metastatic B16BL6 cells, metastatic potential, and the injected number of the cells was exami ned, since the smaller the number of tumor cells injected, the more clearly the immune defense may be observed. When 1 x 10(6) or 1 X 10(5) B16BL6 cel ls were injected into mice via the tail vein, both numbers of cells accumul ated in the lung at a similar rate: there nas an approximately 10-fold diff erence in the number of accumulated cells between the two doses. Eliminatio n from the lung was not dependent on the cell number but on the proportion of accumulated cells. However, the injection of 1 X 10(4) cells resulted in lung accumulation less than one-tenth of that obtained with 1 X 10(5) cell injection. Metastasis was observed when 1 X 10(5) or 1 X 10(6) B16BL6 cell s were injected, but not after injection of 1 X 10(4) cells. To clarify the roles of the immune defense system at the initial phase of metastasis, we challenged macrophage-depleted mice with 1 X 10(4) tumor cells. Treatment o f mice with 2-chloroadenosine prior to the tumor cell challenge cancelled t he suppression of not only metastasis but also the lung accumulation, Furth ermore, the administration of 2-chloroadenosine following the tumor cell ch allenge had little effect on the metastatic potential. These results sugges t that the immune surveillance whose action was obvious at the low dose of challenged tumor cells functions strongly at the initial phase but not at t he advanced stages of the metastatic process, and that macrophages play an important role in the suppression of metastasis. (C) 2000 Federation of Eur opean Biochemical Societies.