Transforming growth factor-beta: a bidirectional regulator of hematopoietic cell growth.
Keller JR., Jacobsen SE., Dubois CM., Hestdal K., Ruscetti FW.
It is now apparent that the transforming growth factor-beta (TGF-beta) family of proteins has potent hematopoietic regulatory properties ranging from effects on the growth and differentiation of primitive stem cells to the differentiated functions of mature cells. Although most reports have described the inhibitory activities of TGF-beta on hematopoiesis, recent evidence supports the concept that TGF-beta can have both inhibitory and stimulatory actions on these systems. These differences depend on the differentiation state of the target cell and the other cytokines interacting with the cell. Furthermore, TGF-beta has direct bidirectional effects on cell surface expression of many cytokine receptors suggesting that it is part of the mechanism of action of TGF-beta. The major biological effect of TGF-beta on hematopoietic cell growth is the reversible inhibition of entry into the cell cycle. Importantly, the effect of in vivo administration of TGF-beta has mimicked the in vitro effects. Ultimately, well designed clinical trials will determine whether the exciting potential of TGF-beta can be used to treat or prevent myelotoxicity and other bone marrow dysfunctions.