Bone marrow matrix promotes differentiation and prolongs the cell cycle of U-937 cells

The extracellular matrix influences the growth and differentiation of a variety of cell types. In this study, the effects of bone marrow extracellular matrix on U-937 cells, a human histiocytic lymphoma cell line, were assessed. Sixty percent of U-937 cells adhered to extracellular matrix, whereas only 1% adhered to uncoated plastic. U-937 cells grown on extracellular matrix released significantly more lysozyme into the medium (8.3 ± 0.3μng/10⁶ cells) compared to those grown on plastic (4.2 ± 0.5 μg/10⁶ cells). FMLP (f-metleu-phe) receptor expression was also enhanced suggesting a more mature phenotype in cells grown on matrix (2980 cpm/10⁶ cells vs 230 cpm/10⁶ cells on plastic). Furthermore, bone marrow extracellular matrix inhibited proliferation of U-937 cells. After four days in culture, there was a 65% inhibition of cell growth in matrix-coated flasks compared to uncoated flasks. Since an arrest in G₀/G₁, usually precedes mammalian cell differentiation, DNA histograms were performed on U-937 cells grown on matrix to detect such an arrest. However, the cell cycle distribution of U-937 cells grown on extracellular matrix or uncoated plastic for various time periods was similar. In contrast, bromodeoxyuridine pulse labeling revealed approximately a 5 hr prolongation in cycle length in cells grown on extracellular matrix. We conclude that bone marrow extracellular matrix induced macrophage-like differentiation and inhibited proliferation of U-937 cells with a prolongation of the cell cycle that was not G₀/G₁ phase specific.