Regulation of the growth and production of granulocyte colony-stimulating activity (CSA) by WEHI-3 cells, a lysozyme-secreting mouse cell line adapted to culture, was investigated in vitro. WEHI-3 cloning efficiency is not enhanced by exogenously added CSA. However, WEHI-3 cloning efficiency in agar was suppressed by an activity in human polymorphonuclear neutrophil extract (colony-inhibiting activity) which inhibits endogenous WEHI-3 CSA production. The addition of increasing concentrations of WEHI-3- or L cell-conditioned medium containing CSA to CIA-depressed WEHI-3 agar cultures resulted in graded increases of cloning efficiency to that of the untreated sample. Testosterone, Deca-Durabolin, and bacterial lipopolysaccharide increased production of CSA by WEHI-3 cells and overcame colony-inhibiting activity-mediated suppression of CSA production, even when activating agents were added 1 day after the addition of colony-inhibiting activity. The activating agents had no direct stimulatory effect on normal mouse marrow colony-forming cells and did not enhance CSA activity. WEHI-3 cells respond to growth inhibitory and stimulatory activities and can serve as an in vitro model for studying the regulation of neoplastic cells.
This work was supported in part by National Cancer Institute Grants CA-08748, CA-17353, and CA-17085, National Science Foundation Grant BMS 75-19734, and the Gar Reichman Foundation.