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

Document Type

Article

Abstract

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.

Medical Subject Headings

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

Publication Date

7-1-2021

Publication Title

Clinical and translational science

E-ISSN

1752-8062

Volume

14

Issue

4

First Page

1265

Last Page

1271

PubMed ID

33566445

Digital Object Identifier (DOI)

10.1111/cts.12978

This document is currently not available here.

Share

COinS