Transforming growth factor-beta 1 modulates the effect of 1 alpha, 25-dihydroxyvitamin D3 on leukemic cells.

The human leukemic cells HL-60, U937, KG-1 and THP-1 incubated with transforming growth factor-beta 1 (TGF-beta 1) were studied by examining cell surface antigens and macrophage-specific activities. The addition of 0.5 ng/ml (20 pM) of TGF-beta 1 with 1 alpha, 25-dihydroxyvitamin D3 [1 alpha, 25(OH)2D3] induced more Leu-M3 (CD14)-positive cells (approximately 80%) than 5 X 10(-8) M 1 alpha, 25(OH)2D3 alone did (30 to 50%), although original HL-60 cells did not express any Leu-M3 antigen at all. Tumor necrosis factor-alpha (TNF-alpha) with TGF-beta 1 and 1 alpha, 25(OH)2D3 was found to potentiate the expression of these surface antigens. Furthermore, the phagocytic activity was also induced strongly. The expression of CR3 (CD11b) antigen was also increased, and all Leu-M3-positive cells were found CR3-positive when HL-60, U937, and THP-1 cells were treated with these stimulants. In contrast, CR3 but not Leu-M3 was induced in KG-1 cells after the same treatment. This may indicate that the responsiveness of leukemic cells to TGF-beta 1 and 1 alpha, 25(OH)2D3 might vary depending on a differentiation stage of the target cells. Furthermore, K562 cells originated from a more undifferentiated precursor, were not able to respond to these two inducers. These results suggested that some of TGF-beta superfamily proteins might represent potent modulators in hematopoiesis, especially in the development of monocytes-macrophages or their precursors.