Angulin-1/LSR inhibition transiently disrupts the blood-tumor barrier to enhance doxil permeability and impair malignant glioma progression.

ABSTRACT: The blood-tumor barrier (BTB) prevents effective central nervous system (CNS) drug delivery, especially in malignant gliomas. Brain endothelium predominates the BTB and connects through bicellular and tricellular tight junctions (TJ). Angulin-1/LSR, is a highly expressed endothelial tricellular TJ. Our studies explore the role of Angubindin-1, an Angulin-1/LSR binder, to disrupt tricellular TJ integrity, increase drug entry and hamper glioma progression. Using rat brain endothelial cells (RBMVEC) we tracked Angulin-1/LSR localization and expression to the membrane; binding tightest to Angubindin-1 2-8 hours post-treatment ( p < 0.05). Angubindin-1 dose-dependently reduced bicellular and tricellular TJs 1-4 hours post treatment ( p < 0.05), returning to baseline by 24 hours (

SUBMITTER: Ferguson D 

PROVIDER: S-EPMC12324529 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature