The influence of vascular endothelial growth factor on secretion of interleukin-6 of bone marrow stromal cells in multiple myeloma

Objective Through studying the effects of vascular endothelial growth factor(VEGF)on bone marrow stromal cells(BMSCs),to focus on the secretion of interleukin-6(IL6)and to analyze the role of VEGF in the pathogenesis.Methods Bone marrow samples were obtained from 18patients.8 cases of Iron Deficiency Anemia(IDA) were served as normal control.MM patient and normal control BMSCs(MM BMSCs and N-BMSCs) were isolated and cultured routinely in vitro.For stimulation experiments,BMSCs were in passage 2 and 3.MM-BMSCs were stimulated with different concentrations of recombinant human VEGF or VEGF100μg/L for different time.ELISA was performed to detect the secretion of IL-6 in culture supernatants of BMSCs.Results Adherent BMSCs were mostly CD54 + fibroblast-like cells.Notably,basal IL-6 concentrations in MM-BMSCs tended to be higher than in N-BMSCs,P0.05.IL-6 concentrations were determined in culture supernatants of MM-BMSCs after stimulation with different concentration VEGF or VEGF for different time.The VEGF induced a time-and dose-dependent increase in IL-6 secretion by MM-BMSCs.Analysis of significance for overall group differences was performed that indicated dose-and time-dependent increase in IL-6 secretion(P0.05).Conclusion IL-6 and VEGF are very important cytokines in MM growth and infiltration.It is conceivable that the stromal cell compartment may,in response to angiogenic factors,release cytokines capable of sustaining tumor growth.The findings suggest that VEGF is a paracrine mediator supporting myeloma cell growth through the induction of IL-6 release by bone marrow stroma.