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We have recently demonstrated that transforming growth factor (TGF)-beta 1 and TGF-beta 2 are potent inhibitors of the growth and differentiation of murine and human hematopoietic cells. The proliferation of primary unfractionated murine bone marrow by interleukin-3 (IL-3) and human bone marrow by IL-3 or granulocyte/macrophage colony-stimulating factor (GM-CSF) was inhibited by TGF-beta 1 and TGF-beta 2, while the proliferation of murine bone marrow by GM-CSF or murine and human marrow with G-CSF was not inhibited. Mouse and human hematopoietic colony formation was differentially affected by TGF-beta 1. In particular, CFU-GM, CFU-GEMM, BFU-E, and HPP-CFC, the most immature colonies, were inhibited by TGF-beta 1, whereas the more differentiated unipotent CFU-G, CFU-M, and CFU-E were not affected. TGF-beta 1 inhibited IL-3-induced growth of murine leukemic cell lines within 24 h, after which the cells were still viable. Subsequent removal of the TGF-beta 1 results in the resumption of normal growth. TGF-beta 1 inhibited the growth of factor-dependent NFS-60 cells in a dose-dependent manner in response to IL-3, GM-CSF, G-CSF, CSF-1, IL-4, or IL-6. TGF-beta 1 inhibited the growth of a variety of murine and human myeloid leukemias, while erythroid and macrophage leukemias were insensitive. Lymphoid leukemias, whose normal cellular counterparts were markedly inhibited by TGF-beta, were also resistant to TGF-beta 1 inhibition. These leukemic cells have no detectable TGF-beta 1 receptors on their cell surface. Last, TGF-beta 1 directly inhibited the growth of isolated Thy-1-positive progenitor cells. Thus, TGF-beta may be an important modulator of normal and leukemic hematopoietic cell growth.
J R Keller, and
G K Sing, and
L R Ellingsworth, and
F W Ruscetti
January 1990,
Biotherapy (Dordrecht, Netherlands),
J R Keller, and
G K Sing, and
L R Ellingsworth, and
F W Ruscetti
June 1988,
British journal of cancer,
J R Keller, and
G K Sing, and
L R Ellingsworth, and
F W Ruscetti
January 1995,
The Journal of hand surgery,
J R Keller, and
G K Sing, and
L R Ellingsworth, and
F W Ruscetti
October 1990,
Blood,
J R Keller, and
G K Sing, and
L R Ellingsworth, and
F W Ruscetti
March 1989,
Experimental hematology,
J R Keller, and
G K Sing, and
L R Ellingsworth, and
F W Ruscetti
April 1995,
Cancer research,
J R Keller, and
G K Sing, and
L R Ellingsworth, and
F W Ruscetti
January 1987,
Journal of cellular physiology. Supplement,
J R Keller, and
G K Sing, and
L R Ellingsworth, and
F W Ruscetti
January 1992,
International journal of cell cloning,
J R Keller, and
G K Sing, and
L R Ellingsworth, and
F W Ruscetti
November 1991,
Journal of cellular biochemistry,
J R Keller, and
G K Sing, and
L R Ellingsworth, and
F W Ruscetti
September 1992,
Leukemia,
