Human colony-stimulating activity-producing tumor: production of very low mouse-active colony-stimulating activity and induction of marked granulocytosis in mice.

We reported previously a human lung cancer which induced marked granulocytosis both in the patient and in the tumor-transplanted nude mice (G-1 mice), and whose conditioned media (G-1-T-CM) contained both human-active colony-stimulating activity (h-CSA) (810 colonies/ml) and mouse-active colony-stimulating activity (m-CSA) (530 colonies/ml), suggesting that the CSA produced by the tumor caused granulocytosis both in the patient and in G-1-mice. We reported here another human lung cancer which induced marked granulocytosis both in the patient and in the tumor-transplanted nude mice (G-2-mice). However, in contrast to the tumor reported by us previously, the conditioned media of this tumor (G-2-T-CM) contained only very weak m-CSA (86 colonies/ml), although h-CSA was very strong (7332 colonies/ml). The ratio of m-CSA to h-CSA in G-1-T-CM (0.654) was 55-fold higher than that in G-2-T-CM (0.012). Gel filtration of G-2-T-CM on a Sephadex G-150 column denied the presence of colony-inhibiting activity which inhibited m-CSA in G-2-T-CM. Since the addition of serum obtained from G-2 mice did not enhance m-CSA in G-2-T-CM, it seems unlikely that the G-2 tumor produced an inactive form of m-CSA which was activated in G-2 mouse serum. G-2-T-CM tended to maintain the number of colony-forming units in spleen in mouse bone marrow during liquid cultures, while G-1-T-CM did not. These results may indicate that the G-2 tumor produced a humoral factor which has very weak CSA and acts on stem cells rather than on committed progenitors.