Dopamine regulates endothelial progenitor cell mobilization from mouse bone marrow in tumor vascularization
Dopamine regulates endothelial progenitor cell mobilization from mouse bone marrow in tumor vascularization
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DOI：
10.1172/jci33125
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发表时间：
2008-04-01
影响因子：
15.9
通讯作者：
Basu, Sujit
中科院分区：
文献类型：
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作者：
Chakroborty, Debanjan;Chowdhury, Uttio Roy;Basu, Sujit
从骨髓中动员内皮祖细胞（EPCs）及其随后参与新生血管形成与肿瘤生长和新生血管形成有关。由于神经递质多巴胺（DA）调节成人内皮细胞的功能，我们假设DA可能有一个调节作用，动员EPCs从骨髓龛。我们发现，有一个显着的骨髓DA含量下降，EPC动员与肿瘤新生血管的荷瘤小鼠增加。DA治疗荷瘤小鼠通过其D-2受体抑制EPC动员和肿瘤生长，因为DA治疗未能抑制用特异性DA D-2受体拮抗剂治疗的荷瘤小鼠和缺乏D-2受体的荷瘤小鼠中的EPC动员。此外，我们发现DA通过D-2受体，通过抑制VEGF诱导的ERK 1/ERK 2磷酸化和MMP-9的合成，对EPC动员产生抑制作用。这些发现揭示了DA和EPC动员之间的新联系，并提出了DA和D-2药物在治疗癌症和其他涉及新血管形成的疾病中的新用途。
Mobilization of endothelial progenitor cells (EPCs) from the bone marrow and their subsequent participation in neovessel formation are implicated in tumor growth and neovascularization. As the neurotransmitter dopamine (DA) modulates adult endothelial cell function, we hypothesized that DA might have a regulatory role in mobilization of EPCs from the bone marrow niche. We show that there was a significant decrease in bone marrow DA content and an increase in EPC mobilization in tumor-bearing mice associated with tumor neovascularization. DA treatment of tumor-bearing mice inhibited EPC mobilization and tumor growth through its D-2 receptors, as DA treatment failed to inhibit EPC mobilization in tumor-bearing mice treated with a specific DA D-2 receptor antagonist and in tumor-bearing mice lacking the D-2 receptor. In addition, we found that DA, through D-2 receptors, exerted its inhibitory effect on EPC mobilization through suppression of VEGFA-induced ERK1/ERK2 phosphorylation and MMP-9 synthesis. These findings reveal a new link between DA and EPC mobilization and suggest a novel use for DA and D-2 agents in the treatment of cancer and other diseases involving neovessel formation.