期刊
CANCER RESEARCH
卷 64, 期 16, 页码 5551-5555出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-04-1600
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- NCI NIH HHS [CA78383] Funding Source: Medline
- NHLBI NIH HHS [HL72178, HL70567] Funding Source: Medline
Many important physiological and pathological processes are modulated by angiogenesis. It has been shown that initiation of this angiogenic process is an essential early step in the progression of malignant tumors. We report here that ablation of peripheral dopaminergic nerves markedly increased angiogenesis, microvessel density, microvascular permeability, and growth of malignant tumors in mice. Endogenous peripheral dopamine acted through D-2 receptors as significantly more angiogenesis and tumor growth was observed in D-2 dopamine receptor knockout mice in comparison with controls. The vascular endothelial growth factor receptor 2 phosphorylation, which is critical for promoting angiogenesis, was also significantly more in tumor endothelial cells collected from the dopamine-depleted and D-2 dopamine receptor knockout animals. These results reveal that peripheral endogenous neurotransmitter dopamine might be an important physiological regulator of vascular endothelial growth factor-mediated tumor angiogenesis and growth and suggest a novel link between endogenous dopamine, angiogenesis, and tumor growth.
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