Lipopolysaccharide Effect on Vascular Endothelial Factor and Matrix Metalloproteinases in Leukemic Cell Lines In vitro

BACKGROUND Angiogenesis, the process of new vessels generation, plays a critical role in tumor invasion and metastasis. Vascular Endothelial Growth Factor (VEGF), as a cytokine, and Matrix Metalloproteinases (MMPs), has been the important factors that involved in angiogenesis. Lipopolysaccharide (LPS) has an essential effect on angiogenesis. OBJECTIVES In this study the effect of LPS on VEGF production and MMP-2/MMP-9 activity in two leukemic cell lines has been assessed in vitro. MATERIALS AND METHODS Human leukemic U937 and THP1 cells were cultured in complete RPMI medium. Then the cells at the exponential growth phase were incubated with different concentrations of LPS (0 - 4 μg/mL) for 48 hours. Then the level of VEGF production and MMP-2/MMP-9 activity in cell culture supernatants were evaluated with the ELISA standard kits and gelatin zymography respectively. RESULTS U937 cells have produced a large amount of VEGF without any stimulus and LPS has not shown any substantial effect on VEGF production by these cells. However THP1 cells have produced a small amount of VEGF without stimulation and LPS significantly has increased VEGF production in these cells dose-dependently. Moreover LPS significantly has augmented the MMP-2/MMP-9 activity in the both leukemic cell lines in a dose-dependent manner. CONCLUSIONS Our results have shown that LPS might be a potential inducer/enhancer of VEGF production and MMP-2/MMP-9 activity (angiogenic factors) in leukemia. Moreover the LPS effect on angiogenesis might be in part, due to its stimulatory effects on VEGF and MMPs. Overall LPS-stimulated leukemic cells might be good models for study and planning the useful therapeutic approaches for angiogenesis- dependent diseases.