The Expression And Effect Of Neuropilin In Acute Myeloid Leukemic Cells

Neuropilin (NRP) is a multifunctional receptor for Semaphorin and VEGF₁₆₅. NRP includes NRP-1 and NRP-2. Although NRP was initially described as a mediator of neuronal guidance, it appears to be a mediator of angiogenesis. NRP is expressed in endothelial cells and enhances VEGF₁₆₅ binding to VEGFR2, acting as a co-receptor for VEGFR2. In addition, emerging evidence indicate that many tumor cell types express NRP in vitro and in vivo. NRP interacts with VEGF₁₆₅ and plays important roles in modulating the growth, migration and apoptosis/survival of tumors as well as tumor angiogenesis. The aims of this study are 1) to study the expression of NRP-1 and NRP-2 in human leukemic cell lines, including KG1a, NB4, HL60, U937, HEL, MEG01 and K562, and observe the effects of reducing NRP-1 expression, by RNA interference, on growth, proliferation and migration in HEL cells. 2) to study the expression of NRP-1 and NRP-2 in freshly isolated leukemic cells and the correlation with the clinical features.In this study, we investigated the expression of NRP-1 mRNA in 7 human leukemic cell lines with RT-PCR and study the effects of inhibiting NRP-1 expression on the growth, proliferation and migration in HEL cells by siRNA interference. We found that NRP-1 mRNA was expressed in 6 of 7 luekemic cell lines and NRP-2 was expressed in 3 of 7 cell lines studied. The expression of NRP-1 mRNA in HEL cells was significantly decreased after transfected with siRNA targeting NRP-1 (si-NRP-1) for 24 and 48 hours compared with the control. The expression of NRP-1 protein was also silenced at 24 hours. The viable HEL cells and MTT unit was not different between the si-NRP-1 transfected cells and control cells at 24h, 48h and 72h time points. However, the proliferation increased significantly in control cells after...