Quantitative protein expression of blood-brain barrier transporters in the vasculature of brain metastases of patients with lung and breast cancer

Clin Transl Sci. 2021 Jul;14(4):1265-1271. doi: 10.1111/cts.12978. Epub 2021 Feb 10.


This study determined absolute transporter protein abundances in isolated microvessels of human noncancerous cerebral cortex as well as brain metastases of patients with lung and breast cancer, using a validated targeted proteomics approach. As compared with those in microvessels of noncancerous cerebral cortex, the median protein abundances of glucose transporter 1 (a brain endothelial marker) and sodium-potassium pump (Na/K ATPase, a plasma membrane marker) were decreased by ~ 80% in brain metastasis microvessels. The major efflux transporters (ABCB1 and ABCG2) fell to undetectable in microvessels of more than 80% of brain metastasis specimens. Monocarboxylate transporter 1 was undetectable in microvessels of more than 80% of brain metastases, whereas large neutral amino acid transporter 1 levels remained unchanged. In conclusion, the integrity of the physical and biochemical barrier with respect to transporter protein expression is largely disrupted in brain metastasis tumor vasculatures. Differential transporter protein abundances at the blood-brain barrier and blood-brain tumor barrier provided mechanistic and quantitative basis for prediction of heterogeneous drug penetration into human brain and brain tumors, which is critical not only to the understanding of the success or failure of systemic chemotherapy in the treatment of brain tumors but also to the development of more effective therapeutic strategies.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Blood-Brain Barrier / metabolism
  • Blood-Brain Barrier / pathology
  • Brain Neoplasms / diagnosis
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / secondary
  • Breast Neoplasms / pathology*
  • Cerebral Cortex / blood supply
  • Cerebral Cortex / pathology
  • Child
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Lung Neoplasms / pathology*
  • Male
  • Membrane Transport Proteins / analysis
  • Membrane Transport Proteins / metabolism*
  • Microvessels / metabolism
  • Microvessels / pathology
  • Middle Aged


  • Antineoplastic Agents
  • Membrane Transport Proteins