ISSN:
0730-2312
Keywords:
hematopoiesis
;
transforming growth factor β
;
colony-stimulating factors
;
leukemic cells
;
interleukin-3
;
Life and Medical Sciences
;
Cell & Developmental Biology
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
Notes:
We have recently demonstrated that transforming growth factor (TGF)-β1 and TGF-β2 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-β1 and TGF-β2, 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-β1. In particular, CFU-GM, CFU-GEMM, BFU-E, and HPP-CFC, the most immature colonies, were inhibited by TGF-β1, whereas the more differentiated unipotent CFU-G, CFU-M, and CFU-E were not affected. TGF-β1 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-β1 results in the resumption of normal growth. TGF-β1 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-β1 inhibited the growth of a variety of murine and human myeloid leukemias, while erythorid and macrophage leukemias were insensitive. Lymphoid leukemias, whose normal cellular counterparts were markedly inhibited by TGF-β, were also resistant to TGF-β1 inhibition. These leukemic cells have no detectable TGF-β1 receptors on their cell surface. Last, TGF-β1 directly inhibited the growth of isolated Thy-1-positive progenitor cells. Thus, TGF-β may be an important modulator of normal and leukemic hematopoietic cell growth.
Additional Material:
2 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/jcb.240390209
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