Lipopolysaccharide effect on vascular endothelial factor and matrix metalloproteinases in leukemic cell lines In vitro

Abstract

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.