Neuropilin-1 in acute myeloid leukemia: Expression and role in proliferation and migration of leukemia cells

Neuropilin-1 in acute myeloid leukemia: Expression and role in proliferation and migration of leukemia cells
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DOI:
10.1080/10428190701809149
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发表时间:
2008-01-01
影响因子:
2.6
通讯作者:
Han, Zhong Chao
Han, Zhong Chao
中科院分区:
医学4区
文献类型:
--
作者:
Lu, Lin;Zhang, Lei;Han, Zhong Chao

文献摘要

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神经纤毛蛋白-1(NRP-1)是一种新的血管内皮生长因子(VEGF)受体,在内皮细胞和肿瘤细胞中均有表达。NRP-1在白血病生长和进展中的作用尚不清楚。本实验研究了NRP-1在白血病细胞中的mRNA表达及其作用。我们的研究结果表明,NRP-1 mRNA的表达在6的7个白血病细胞系和原发性白血病来自所有24例急性髓性白血病(AML)患者。通过RNA干扰减少NRP-1表达导致急性髓性白血病细胞系HEL中VEGF介导的促有丝分裂和迁移反应减少。NRP-1表达的增加与AML患者外周血和骨髓中的原始细胞百分比直接相关。我们的数据表明,更高水平的NRP-1的mRNA表达在白血病和NRP-1促进白血病细胞的增殖和趋化反应的VEGF。抑制NRP-1功能可能为AML的治疗提供新的治疗策略。
Neuropilin-1 (NRP-1) is a novel receptor of vascular endothelial growth factor (VEGF) and expressed in endothelial cells and tumor cells. The role of NRP-1 in the growth and progression of leukemia is unknown. Here we studied the mRNA expression and effect of NRP-1 in leukemic cells. Our results showed that NRP-1 mRNA was expressed in six of seven leukemic cell lines and primary leukemias derived from all 24 patients with acute myeloid leukemia (AML). Reduced NRP-1 expression by RNA interference led to a decrease of VEGF-mediated mitogenic and migration responses in acute myeloid leukemic cell line HEL. Increased NRP-1 expression was directly correlated with the blast percentage in both peripheral blood and bone marrow of AML patients. Our data demonstrated that a higher level of NRP-1 mRNA was expressed in leukemias and NRP-1 promoted proliferation and chemotaxis of leukemic cells in response to VEGF. Inhibition of NRP-1 functions may provide a new therapeutic strategy for treatment of AML.