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Dopamine Prevents Ultraviolet B-induced Development and Progression of Premalignant Cutaneous Lesions through its D2

Kai Lu1, Madhavi Bhat1, Sara Peters1

  • 1Department of Pathology, Ohio State University, Columbus, Ohio.

Cancer Prevention Research (Philadelphia, Pa.)
|April 13, 2021
PubMed

Insights

Dopamine (DA) D2 receptor stimulation in endothelial cells reduced skin tumors and squamous cell carcinoma in mice. This suggests DA D2 receptors play a key role in preventing premalignant skin lesion progression.

Area of Science:

  • Oncology
  • Dermatology
  • Neuropharmacology

Background:

  • The role of dopamine (DA) in malignant tumors is known, but its function in premalignant lesions remains unclear.
  • Ultraviolet B (UVB) radiation is a known carcinogen that induces skin lesions and promotes skin cancer development.

Purpose of the Study:

  • To investigate the role of dopamine D2 receptors in the pathogenesis and progression of UVB-induced premalignant skin lesions.
  • To determine if dopamine D2 receptor stimulation can prevent the development of squamous cell carcinoma.

Main Methods:

  • Utilized a mouse model of UVB-induced cutaneous lesions.
  • Administered DA D2 receptor agonists and antagonists to assess their effects on lesion development.
  • Analyzed tumor number, tumor burden, and the incidence of malignant squamous cell carcinoma.
  • Investigated the impact of DA D2 receptor stimulation on VEGFA-dependent proangiogenic genes in vitro and in vivo.

Main Results:

  • Stimulation of DA D2 receptors in endothelial cells significantly reduced tumor number, tumor burden, and malignant squamous cell carcinoma in UVB-exposed mice.
  • DA D2 receptor agonist inhibited VEGFA-dependent proangiogenic genes both in vitro and in vivo.
  • Pretreatment with a selective DA D2 receptor antagonist blocked the agonist's effects, confirming the D2 receptor-mediated action.

Conclusions:

  • This study is the first to report dopamine-mediated regulation of UVB-induced premalignant skin lesion pathogenesis and progression.
  • Dopamine, acting through D2 receptors on endothelial cells, inhibits the development and progression of premalignant skin lesions.
  • Targeting dopamine D2 receptors presents a potential strategy for preventing squamous cell carcinoma of the skin.

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