Growth characteristics of a mouse plasma cell tumor.

Abstract

Summary A quantitative spleen-colony assay was developed and used to evaluate the growth characteristics of the Adj. PC-5 colony-forming units (CFU). There was a positive correlation between the number of colonies per spleen and the number of tumor cells injected, which is compatible with the assumption that each colony arises from one malignant cell. At 21 days, each colony contains 8.4 ± 2.1 × 107 cells, but less than 4.4% of these are tumor stem cells with the proliferative capacity to form a colony. The growth rate of tumor CFU was estimated in the spleen (CFU TD = 20 ± 4 hours) and femoral marrow (CFU TD = 29 ± 5 hours). A survival TD of 36 ± 2 hours was estimated from the survival of mice injected with graded numbers of tumor cells as an indication of the growth rate of the total tumor. The proliferative capacity of the tumor CFU was completely suppressed during a 10-hour exposure to vinblastine in vivo. This result suggests that the majority of tumor CFU have a TG of less than 10 hours. All of the tumor CFU appear to be in cell cycle, for no detectable tumor CFU survived a 10-hour exposure to vinblastine, and 70% of these cells were killed by a 20-minute exposure to tritiated thymidine in vitro. Based on these findings, a model is proposed for the growth kinetics of this tumor. The model states that a small fraction of the tumor population is composed of cells in a short generation cycle with unlimited proliferative capacity (i.e., tumor stem cells). The remaining tumor cells lack the proliferative capacity to form a colony. This model for the Adj. PC-5 tumor is compared with that of a transplantable AKR lymphoma, and the chemotherapeutic implications are discussed.