Reduced tumor growth in a mouse model of schizophrenia, lacking the dopamine transporter

Masanori Asada, Satoru Ebihara, Yohtaro Numachi, Tatsuma Okazaki, Shinsuke Yamanda, Kazutaka Ikeda, Hiroyasu Yasuda, Ichiro Sora, Hiroyuki Arai

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)

Abstract

The incidence of cancer in patients with schizophrenia has been reported to be lower that in the general population. On the other hand, it is well established that patients with schizophrenia have a hyper-dopaminergic system and dopamine has the ability to inhibit tumor angiogenesis. Therefore, in order to investigate the molecular mechanisms responsible for the lower cancer risk in schizophrenic patients, we used a mouse model of schizophrenia, which shows hyper-dopaminergic transmission in the nerve terminals of dopaminergic neurons. Here, we hypothesized that tumor growth was reduced in a mouse model of schizophrenia, lacking the dopamine transporter (DAT), and investigated tumor growth and angiogenesis in DAT knockout mice. The subcutaneous tumor in mice inoculated with cancer cells was smaller in DAT-/- mice than in the wild type (p < 0.05); however, the level of plasma dopamine in DAT -/- mice was lower than that of control littermates. Using human umbilical vascular endothelial cells (HUVEC), we examined dopamine signaling through dopamine D1 receptor (D1R) and D2R. Dopamine stimulation slightly decreased the surface expression of vascular endothelial growth factor receptor-2 (VEGF-R2) but induced the phosphorylation of VEGF-R2 through Src in HUVEC. In addition, DAT-/- mice had less D1R. Both pharmacological and genetic interruption of D1R showed inhibited tumor growth. These results suggest that modulation of the dopaminergic system may contribute to cancer therapy.

Original languageEnglish
Pages (from-to)511-518
Number of pages8
JournalInternational Journal of Cancer
Volume123
Issue number3
DOIs
Publication statusPublished - 2008 Aug 1

Keywords

  • Angiogenesis
  • Dopamine
  • Dopamine receptors
  • Dopamine transporter
  • Schizophrenia
  • VEGF-R2

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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