Suppressive effects of neuroblastoma cells and conditioned media on in vitro granulopoiesis

Bone marrow is the commonest site of metastasis in neuroblastoma. This results in minimal to total bone marrow suppression. To establish the mechanism of neuroblastoma suppression of granulopoiesis, the effects of murine C-1300 neuroblastoma cells on granulopoietic activity of normal syngeneic mice was examined. Using a double layer agar system, intact tumor cells, media conditioned by the culture of neuroblastoma cells (NCM) and homogenate of these cells were found to have significant suppressive effects on granulocyte macrophage colony formation (CFU-GM). The rate of production of the NCM was gradual, reaching a plateau by day 4 of the culture. No cell-cell contact was necessary to elicit the CFU-GM depression i.e. regardless of the location of the intact tumor cells or their homogenate in the same or separate layer of the culture, there was a significant linear suppression of CFU-GM (p less than .0005). This suppression proved to be dose dependent. NCM also caused a similar decline in colony formation (p less than 0.005) indicating the suppression is due to diffusible factor(s). The CFU-GM suppressive factor(s) are not dialyzable and cannot withstand 56 degrees C for 15 min. The granulopoietic suppression seen in neuroblastoma may be, at least in part, due to the suppressive effects of these factor(s).