Transforming growth factor β: Possible roles in the regulation of normal and leukemic hematopoietic cell growth

✍ Scribed by Jonathan R. Keller; Garwin K. Sing; Larry R. Ellingsworth; Francis W. Ruscetti

• Publisher: John Wiley and Sons
• Year: 1989
• Tongue: English
• Weight: 610 KB
• Volume: 39
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.240390209

✦ Synopsis

We have recently demonstrated that transforming growth factor (TGF)-Pl and TGF-02 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-01 and TGF-02, 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-@1 . In particular, CFU-GM, CFU-GEMM, BFU-E, and HPP-CFC, the most immature colonies, were inhibited by TGF-01, whereas the more differentiated unipotent CFU-G, CFU-M, and CFU-E were not affected. TGF-01 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-01 results in the resumption of normal growth. TGF-01 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-01 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-0, were also resistant to TGF-P1 inhibition. These leukemic cells have no detectable TGF-01 receptors on their cell surface. Last, TGF-01 directly inhibited the growth of isolated Thy-1-positive progenitor cells. Thus, TGF-0 may be an important modulator of normal and leukemic hematopoietic cell growth.