Transforming Growth Factor Beta 1 Selectively Regulates Early Murine Hematopoietic Progenitors and Inhibits the Growth of IL-3-dependent Myeloid Leukemia Cell Lines

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 1988 Aug 1

PMID 3261777

Citations 25

Authors

J R Keller

C Mantel

G K Sing

L R Ellingsworth

S K Ruscetti

F W Ruscetti

Affiliations

Soon will be listed here.

Abstract

Transforming growth factor beta 1 (TGF-beta 1) has been shown to be associated with active centers of hematopoiesis and lymphopoiesis in the developing fetus. Therefore, the effects of TGF-beta 1 on mouse hematopoiesis were studied. TGF-beta 1 is a potent inhibitor of IL-3-induced bone marrow proliferation, but it does not inhibit the proliferation induced by granulocyte/macrophage, colony-stimulating factor (CSF), granulocyte CSF, and erythropoietin (Epo). TGF-beta 1 also inhibits IL-3-induced multipotential colony formation of bone marrow cells in soft agar, which includes early erythroid differentiation, while Epo-induced terminal differentiation is unaffected. In addition, IL-3-induced granulocyte/macrophage colonies were inhibited; however, small clusters of differentiated myeloid cells were consistently seen in cultures containing IL-3 and TGF-beta 1. Thus, TGF-beta 1 selectively inhibits early hematopoietic progenitor growth and differentiation but not more mature progenitors. TGF-beta 1 is also a potent inhibitor of IL-3-dependent and -independent myelomonocytic leukemic cell growth, while the more mature erythroid and macrophage leukemias are insensitive. Therefore, TGF-beta 1 functions as a selective regulator of differentiating normal hematopoietic cells, and suppresses myeloid leukemic cell growth.

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References

Stephenson J, AXELRAD A, McLeod D, Shreeve M . Induction of colonies of hemoglobin-synthesizing cells by erythropoietin in vitro. Proc Natl Acad Sci U S A. 1971; 68(7):1542-6. PMC: 389236. DOI: 10.1073/pnas.68.7.1542. View

Massague J . The TGF-beta family of growth and differentiation factors. Cell. 1987; 49(4):437-8. DOI: 10.1016/0092-8674(87)90443-0. View

De Larco J, Todaro G . Growth factors from murine sarcoma virus-transformed cells. Proc Natl Acad Sci U S A. 1978; 75(8):4001-5. PMC: 392918. DOI: 10.1073/pnas.75.8.4001. View

Dexter T, Garland J, Scott D, Scolnick E, Metcalf D . Growth of factor-dependent hemopoietic precursor cell lines. J Exp Med. 1980; 152(4):1036-47. PMC: 2185980. DOI: 10.1084/jem.152.4.1036. View

Burgess A, Metcalf D . The nature and action of granulocyte-macrophage colony stimulating factors. Blood. 1980; 56(6):947-58. View

Oliff A, Ruscetti S, Douglass E, Scolnick E . Isolation of transplantable erythroleukemia cells from mice infected with helper-independent Friend murine leukemia virus. Blood. 1981; 58(2):244-54. View

Ihle J, Keller J, Henderson L, Klein F, Palaszynski E . Procedures for the purification of interleukin 3 to homogeneity. J Immunol. 1982; 129(6):2431-6. View

Roberts A, Frolik C, Anzano M, Sporn M . Transforming growth factors from neoplastic and nonneoplastic tissues. Fed Proc. 1983; 42(9):2621-6. View

Assoian R, Komoriya A, Meyers C, Miller D, Sporn M . Transforming growth factor-beta in human platelets. Identification of a major storage site, purification, and characterization. J Biol Chem. 1983; 258(11):7155-60. View

10.

Lawrence D, Pircher R, Jullien P . Normal embryo fibroblasts release transforming growth factors in a latent form. J Cell Physiol. 1984; 121(1):184-8. DOI: 10.1002/jcp.1041210123. View

11.

Roberts A, Anzano M, Wakefield L, Roche N, Stern D, Sporn M . Type beta transforming growth factor: a bifunctional regulator of cellular growth. Proc Natl Acad Sci U S A. 1985; 82(1):119-23. PMC: 396983. DOI: 10.1073/pnas.82.1.119. View

12.

Seyedin S, Thomas T, Thompson A, Rosen D, Piez K . Purification and characterization of two cartilage-inducing factors from bovine demineralized bone. Proc Natl Acad Sci U S A. 1985; 82(8):2267-71. PMC: 397538. DOI: 10.1073/pnas.82.8.2267. View

13.

Keller J, Weinstein Y, Hursey M, Ihle J . Interleukins 2 and 3 regulate the in vitro proliferation of two distinguishable populations of 20-alpha-hydroxysteroid dehydrogenase-positive cells. J Immunol. 1985; 135(3):1864-71. View

14.

Fine L, HOLLEY R, Nasri H . BSC-1 growth inhibitor transforms a mitogenic stimulus into a hypertrophic stimulus for renal proximal tubular cells: relationship to Na+/H+ antiport activity. Proc Natl Acad Sci U S A. 1985; 82(18):6163-6. PMC: 391012. DOI: 10.1073/pnas.82.18.6163. View

15.

Derynck R, Jarrett J, Chen E, Goeddel D . The murine transforming growth factor-beta precursor. J Biol Chem. 1986; 261(10):4377-9. View

16.

Assoian R, Sporn M . Type beta transforming growth factor in human platelets: release during platelet degranulation and action on vascular smooth muscle cells. J Cell Biol. 1986; 102(4):1217-23. PMC: 2114151. DOI: 10.1083/jcb.102.4.1217. View

17.

Seyedin S, Thompson A, BENTZ H, Rosen D, McPherson J, Conti A . Cartilage-inducing factor-A. Apparent identity to transforming growth factor-beta. J Biol Chem. 1986; 261(13):5693-5. View

18.

Rook A, Kehrl J, Wakefield L, Roberts A, Sporn M, Burlington D . Effects of transforming growth factor beta on the functions of natural killer cells: depressed cytolytic activity and blunting of interferon responsiveness. J Immunol. 1986; 136(10):3916-20. View

19.

Kehrl J, Wakefield L, Roberts A, Jakowlew S, Alvarez-Mon M, Derynck R . Production of transforming growth factor beta by human T lymphocytes and its potential role in the regulation of T cell growth. J Exp Med. 1986; 163(5):1037-50. PMC: 2188095. DOI: 10.1084/jem.163.5.1037. View

20.

Ruscetti S . Employment of a [3H]thymidine-incorporation assay to distinguish the effects of different Friend erythroleukemia-inducing retroviruses on erythroid cell proliferation. J Natl Cancer Inst. 1986; 77(1):241-5. View