Objective: Endothelial progenitor cells (EPCs) contribute to the neovascularization formation of solid tumors,but the function of EPCs in non-Hodgkin lymphoma is unclear.Methods: We first cultured EPCs form human umbilical cord blood mononuclear cells and used cell function assay,cell surface marker to identificate EPCs.NHL subcutaneous tumor models were established and 107 human GFP-labeled EPCs were intravenous infused into nude mice tail vein to understand whether EPCs can recruit into lymphoma and their specific location.Then we used NHL cells supernatant and VEGF as intervention factors to study the effect of NHL supernatant on EPCs by tube formation assay,and detected the effect of NHL supernatant on HDAC7 protein expression in EPCs by Western bloting.We used siRNA technology to silence HDAC7 gene in EPCs,and to test the effect of the HDAC7 silence on the angiogenesis ability of EPCs.Last we used Western blotting and immunofluorescence technique to study the activation of HDAC7 protein and HDAC7 intracellular localization.At the same time,we used VEGF downstream kinases inhibitors to inhibit the expression of kinase downstream respectively,and to study the activation of HDAC7 protein and HDAC7 intracellular localization.Results: EPCs were separated from human umbilical cord blood mononuclear cells and identified as monolayers of cobblestone appearing cells The human GFP-labeled EPCs located around the vessels.The new capillaries increased by time after the infusion of EPCs.NHL cells supernatant could promote the tube formation ability of EPCs,and could activate phosphorylation of HDAC7 protein.HDAC7 genes silence of EPCs can weaken the cells migration and tube formation ability.VEGF-A treatment induced HDAC7 phosphorylation.In response to VEGF-A,HDAC7 in EPCs showed nucleocytoplasmic shuttling.HDAC7 nuclear export first turned up at 30 minutes following VEGF-A treatment,then proportion of cells with HDAC7 cytoplasmic accumulation increased,then gradually relocated in the nucleus and primarily went back to the nucleus after 24 hours of VEGF-A simulation.When EPCs were pretreated with PKD1 inhibitor G(o)6976 at 30 minutes before VEGF-A treatment,HDAC7 phosphorylation was obviously inhibited in dose-dependent manner.Neithor PI3K inhibitor LY294002 nor MEK1/2 inhibitor U0126 had any effect on VEGF-A induced HDAC7 phosphorylation.G(o)6976 also inhibited the nucleocytoplasmic shuttling of HDAC7 induced by VEGF-A.Conclusion: EPCs can be recruited to the lymphoma and participate in angiogenesis; NHL microenvironment can promote angiogenensis of EPCs by activation of HDAC7 protein; VEGF induced an increase of p-HDAC7 and nuclear export in a time-dependent manner,which was partly inhibited by PKD1 inhibitor,but not by PI3K inhibitor or MEK inhibitor.These data imply that EPCs involving in the tumor angiogenesis of NHL might be controlled by VEGF-PKD1-HDAC7 axis.