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Regulation of the Proliferation of the Established Human Monoblast Cell Line, U937, at the Single Cell Level¹

Department of Developmental Hematopoiesis, Memorial Sloan Kettering Cancer Center [E. B.]; Department of Lymphokine Biology, The Lindsley F. Kimball Research Institute of the New York Blood Center, New York, New York 10021 [B. Y. R.]; and Departments of Medicine, Hematology/Oncology, Microbiology and Immunology, Indiana University School of Medicine, Walther Medical Research Institute and the Elks Cancer Research Center, Indianapolis, Indiana 46223 [H. E. B.]

U937 cells, an established monoblast or early monocyte cell line, were assessed as a model in vitro for the regulation of cell growth at the single cell level. Colony formation by 500 U937 cells, preinduced to a state of responsiveness to lactoferrin (LF) by incubation with human interferon was suppressed by LF. LF-suppressed colony formation was restored by partially purified growth activity derived from U937 cells. The release of growth factor(s) into conditioned medium required concentrations of >500 U937 cells/ml and this release was dependent on the length of time that the cells conditioned the culture medium. This release was suppressed by LF. U937 cells were induced to a state of responsiveness to LF by incubation with human interferon, washed, and plated as a single cell per well. Individual cells formed colonies with a cloning efficiency of 50% which equalled the cloning efficiency detected when 500 U937 cells/ml were plated, suggesting that U937 colony forming cells might contain endogenous growth activity. Detection of these endogenous growth activities required the use of LF. The cloning efficiency of individually isolated U937 cells was suppressed by 50% with LF, similar to the LF suppression of colony formation when 500 cells/ml were plated. That the LF-suppressed U937 colony forming cells required growth activity was suggested as the cloning efficiency of LF-suppressed individually isolated U937 colony forming cells was restored by partially purified U937 growth activity. Partially purified U937 growth activity did not stimulate, enhance, or inhibit colony formation by normal human bone marrow granulocyte-macrophage progenitors. U937 cells can thus serve as a useful model for the study of growth regulation at the level of a single cell.

¹ These studies were supported by USPHS Grants CA 36740 (formerly CA 23528), CA 36464 (to H. E. B.) and CA 38661 (to B. Y. R.) from the National Cancer Institute and by a Clinical Scholar Award from Sloan Kettering Institute to E. B.

² To whom requests for reprints should be addressed, at Department of Medicine, Indiana University School of Medicine, Clinical Building, Room 379, 541 Clinical Drive, Indianapolis, IN 46223.

Received 12/20/85. Revised 3/18/86. Accepted 3/21/86.