Dietary Selenium Supplementation Modulates Growth of Brain Metastatic Tumors and Changes the Expression of Adhesion Molecules in Brain Microvessels

Biol Trace Elem Res. 2016 Aug;172(2):395-407. doi: 10.1007/s12011-015-0595-x. Epub 2015 Dec 26.

Abstract

Various dietary agents can modulate tumor invasiveness. The current study explored whether selenoglycoproteins (SeGPs) extracted from selenium-enriched yeast affect tumor cell homing and growth in the brain. Mice were fed diets enriched with specific SeGPs (SeGP40 or SeGP65, 1 mg/kg Se each), glycoproteins (GP40 or GP65, 0.2-0.3 mg/kg Se each) or a control diet (0.2-0.3 mg/kg Se) for 12 weeks. Then, murine Lewis lung carcinoma cells were infused into the brain circulation. Analyses were performed at early (48 h) and late stages (3 weeks) post tumor cell infusion. Imaging of tumor progression in the brain revealed that mice fed SeGP65-enriched diet displayed diminished metastatic tumor growth, fewer extravasating tumor cells and smaller metastatic lesions. While administration of tumor cells resulted in a significant upregulation of adhesion molecules in the early stage of tumor progression, overexpression of VCAM-1 (vascular call adhesion molecule-1) and ALCAM (activated leukocyte cell adhesion molecule) messenger RNA (mRNA) was diminished in SeGP65 supplemented mice. Additionally, mice fed SeGP65 showed decreased expression of acetylated NF-κB p65, 48 h post tumor cell infusion. The results indicate that tumor progression in the brain can be modulated by specific SeGPs. Selenium-containing compounds were more effective than their glycoprotein controls, implicating selenium as a potential negative regulator of metastatic process.

Keywords: Adhesion; Brain; Cell adhesion molecules; NF-κB; Selenium; Tumor progression.

MeSH terms

  • Activated-Leukocyte Cell Adhesion Molecule / genetics
  • Activated-Leukocyte Cell Adhesion Molecule / metabolism
  • Animals
  • Brain / blood supply*
  • Brain / drug effects*
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology*
  • Brain Neoplasms / secondary
  • Carcinoma, Lewis Lung / pathology
  • Cell Adhesion Molecules / metabolism*
  • Dietary Supplements
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microvessels / drug effects*
  • Microvessels / metabolism*
  • Neoplasm Metastasis / drug therapy*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Selenium / administration & dosage
  • Selenium / pharmacology*
  • Selenium / therapeutic use
  • Vascular Cell Adhesion Molecule-1 / genetics
  • Vascular Cell Adhesion Molecule-1 / metabolism

Substances

  • Activated-Leukocyte Cell Adhesion Molecule
  • Cell Adhesion Molecules
  • RNA, Messenger
  • Vascular Cell Adhesion Molecule-1
  • Selenium