Abstract
Thrombospondin-1 (TSP), a multifunctional extracellular matrix protein, modulates human hematopoietic stem cell adherence and thus may play a role in blood cell proliferation and/or differentiation. The expression of TSP was studied in the human myeloid leukemia cell line, HL-60, upon differentiation into monocytes by phorbol-13-monoacetate (PMA) or into granulocytes by all-trans retinoic acid (RA). HL-60 cells cultured under serum-free conditions constitutively secreted low amounts of TSP into the cultured medium, approximately 13 ng/106 cells/24 h. PMA used at 4 × 10−8 Mdid not significantly modulate TSP secretion over a 24 h period. In contrast, RA at 10−7 M induced a 5- to 10-fold increase in TSP secreted by HL-60 cells during their differentiation into granulocytes over a 5 day period. The role of secreted TSP in RA-dependent cessation of growth and differentiation was examined using blocking anti-TSP antibodies. In the presence of the polyclonal anti-TSP antibody R5 (25 μg/ml), growth of RA-treated HL-60 cells was maintained at control levels for up to 3 days and a concomitant delay in granulocytic differentiation was observed. Moreover, the addition of soluble TSP (0.5–5 μg/ml) to untreated HL-60 cells decreased their growth and promoted their differentiation in a dose-dependent manner. Using a neutralizing antibody to transforming growth factor β (TGF-β) or purified TGF-β 1 we further demonstrated that the effects of TSP were not mediated through activation of latent TGF-β. These studies indicate that TSP decreases the proliferation and promotes the differentiation of HL-60 cells.
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Touhami, M., Fauvel-Lafève, F., Silva, N. et al. Induction of thrombospondin-1 by all-trans retinoic acid modulates growth and differentiation of HL-60 myeloid leukemia cells. Leukemia 11, 2137–2142 (1997). https://doi.org/10.1038/sj.leu.2400866
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DOI: https://doi.org/10.1038/sj.leu.2400866