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TGF-beta 1 and TGF-beta 2 are equipotent selective inhibitors of murine and human haemopoiesis in vitro. Primitive haemopoietic cells such as the high proliferative potential progenitor cell and the colony-forming unit (CFU)-GEMM are directly inhibited by TGF-beta whereas the more differentiated CFU-G, CFU-M and CFU-E are not. Recombinant TGF-beta 1 administered intraperitoneally or intravenously to mice selectively inhibits haemopoietic colony formation in a time- and dose-dependent manner to the same extent as seen in vitro. The progenitors are reversibly prevented from entering the cell cycle. This inhibitory action of TGF-beta functions on at least two levels: (1) down-modulation of the cell surface expression of receptors for growth stimulatory molecules and (2) interference with the intracellular signalling pathways of these molecules. In addition, expression of TGF-beta receptors is regulated during cytokine stimulation of haemopoiesis. Neoplastic B lymphocytes can proliferate by escaping from a TGF-beta-mediated autocrine inhibitory loop. Activation signals (e.g. phorbol esters) inhibit tumour cell growth by stimulating active TGF-beta production and inducing cell surface expression of TGF-beta receptors. These results indicate that TGF-beta may be useful as a bone marrow protective and/or an antitumour agent.

Type

Journal article

Journal

Ciba Found Symp

Publication Date

1991

Volume

157

Pages

212 - 227

Keywords

Animals, Antineoplastic Agents, B-Lymphocytes, Cell Cycle, Cells, Cultured, Cytokines, Down-Regulation, Drug Synergism, Granulocyte-Macrophage Colony-Stimulating Factor, Hematopoiesis, Hematopoietic Stem Cells, Humans, Immunologic Factors, Leukemia, Promyelocytic, Acute, Lymphoma, B-Cell, Mice, Neoplastic Stem Cells, Receptors, Cell Surface, Receptors, Transforming Growth Factor beta, Recombinant Proteins, Transforming Growth Factor beta, Tumor Cells, Cultured