HERG K+ Channels Promote Angiogenesis by Enhancing the Expression Level of VEGF in Leukemia Cells in Vitro.

Abstract

Abstract 4818 IntroductionFOur previous studies demonstrated that HERG1 K+ channels are aberrantly expressed in leukemia cells. Recent studies also indicate the leukemia cells to have influence on angiogenesis. If there are any involvements of HERG1 K+ channels on the leukemia-induced angiogenesis are not yet investigated. In this study, the effect of HERG1 K+ channels in K-562 cells on angiogenesis was measured by the proliferation, migration and tube formation of human umbilical vein endothelial cells (HUVECs), acknowledging that these are critical steps for angiogenesis. The possible mechanism of HERG K+ channels on leukemic cells in angiogenesis is also investigated by measuring expression level of VEGF in both K-562 cells and primary leukemic cells. MethodsK-562 cells were cultured in the medium containing various concentration (0,10.20,40uM) of E-4031, a HERG1 K+ chnanel special inhibitor. HUVECs were seeded in the conditional medium and HUVEC proliferation was measured by the CCK-8 cell proliferation assay. HUVEC cell migration was performed by Boyden chamber (Trans-well). The HUVECs were seeded in the up-chamber and the conditional medium was in down-chamber. The angiogenesis of HUVECs cultured in conditional medium were measured by endothelial tube formation in Matrigel in vitro. The role of HERG K+ channels on VEGF secretion by leukemic cells was determined by ELISA and VEGF mRNA expression of leukemic cells were examined by RT-PCR. ResultsThe results showed that blocking HERG K+ channels on K-562 cells could inhibit the capacity of K-562 cells to induce human HUVEC proliferation, migration and tube formation in a concentration manner in vitro. This suggests that HERG1 K+ channels could influence the cross-talk between the leukemic cells and vascular endothelial cells. Further analyses revealed that HERG1 K+ channels can increase the capacity of K-562 cells and primary leukemia cells to produce VEGF with up-regulation of VEGF mRNA. The similar results were also obtained from other tumor cells. ConclusionsWe demonstrated that HERG1 K+ channels on the membrane of leukemic cells have a promoting effect on angiogenesis. The mechanism is that HERG1 K+ channels can increase the level of VEGF expressions. This may be a critical step of HERG1 K+ channels on tumor induced angiogenesis. Disclosures:No relevant conflicts of interest to declare.