Effect And Significance Of Endothelial Progenitor Cells Modulation By Renal Carcinoma Microenvironment On Tumor Neovascularization

Background:Angiogenesis, the formation of new capillaries from preexisting endothelial cells(ECs), is not the only source of tumor neovascularization. Tumor capillaries can arise fromvasculogenesis, which is de novo vessel formation by EPCs.Neovascularization is considered to have an important role in tumorprogression, metastasis, and recurrence.The EPCs were mobilized into the circulation by mobilization factorsreleased from tumor microenvironmentand subsequently entered into kidney via the blood streamand contribute to neovascularization and biological characteristics of the tumor.However, there is no reportshowing the significance of mobilied EPCs in RCC neovascularization. In this study, the orthotopic RCC model was established to investigate thedistribution characteristic of EPCs in RCC progression, and explore its mobilized mechanism and effect in tumor neovascularizationObjective:To determine the distribution characteristic of EPCs in RCC progression, and explore its mobilized mechanism and effect in tumor neovascularization.Materials and methods:Male,BALB/c nude mice were randomly divided into three groups:RCC group, Sham group and Normal group. Mice of three groups were killed respectively at days21,28,35,42,49after RCC group implant ACHN cell line. Peripheral blood (PB), normal kidney tissue (NT), sham-operated kidney tissue (ST), tumor tissue (TT), and adjacent non-malignant kidney tissue (AT) were harvested at days21,28,35,42, and49. Numbers of circulating endothelial progenitor cells (CEPCs), plasma levels of vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1(SDF-1), distribution and numbers of EPCs, mean microvessel density (MVD), and mRNA and protein expression of VEGF, SDF-1, VEGF receptor2(Flk), and SDF-1receptor (CXCR4) were evaluated in relevant tissues.Results:Circulating endothelial progenitor cell (CEPCs) levels and plasma angiogenic factors (VEGF and SDF-1) were higher in PB of the RCC than those in the normal group and positively correlated with each other. EPCs levels in AT were significantly higher than those in TT and NT, which were positively correlated with CEPCs levels. VEGF and SDF-1expression in AT was significantly higher than that in TT and NT. Levels of these angiogenic factors in AT were positively correlated with those in PB. Mean microvessel density (MVD) was higher in AT than in TT, and that in TT was slightly lower than that in NT.Conclusions:VEGF and SDF-1in adjacent tissue play key role in entire mobilized process of EPCs.EPCs promotes the progress of RCC, involving the promotion on neovascularization through releasing angiogenic factors and incorporated into vascular endothelium.