Ablation of peripheral dopaminergic nerves stimulates malignant tumor growth by inducing vascular permeability factor/vascular endothelial growth factor-mediated angiogenesis

Sujit Basu, Chandrani Sarkar, Debanjan Chakroborty, Janice Nagy, Rita Basu Mitra, Partha Sarathi Dasgupta, Debabrata Mukhopadhyay

Research output: Contribution to journalArticlepeer-review

76 Scopus citations

Abstract

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 D2 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 D2 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.

Original languageEnglish (US)
Pages (from-to)5551-5555
Number of pages5
JournalCancer research
Volume64
Issue number16
DOIs
StatePublished - Aug 15 2004

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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