Dual targeting of Angiopoetin-2 and VEGF potentiates effective vascular normalisation without inducing empty basement membrane sleeves in xenograft tumours.

ABSTRACT:

Background

Effective vascular normalisation following vascular endothelial growth factor (VEGF) inhibition is associated with endothelial cell regression leaving empty basement membrane sleeves (BMS). These long-lived BMS permit the rapid regrowth of tumour vasculature upon treatment cessation and promote resistance to VEGF-targeting drugs. Previous attempts at removing BMS have failed. Angiopoietin-2 (Ang2) is a vascular destabilizing factor that antagonises normalisation. We hypothesised that Ang2 inhibition could permit vascular normalisation at significantly reduced doses of VEGF inhibition, avoiding excessive vessel regression and the formation of empty BMS.

Methods

Mice xenografted with human colorectal cancer cells (LS174T) were treated with low (0.5 mg kg(-1)) or hig

SUBMITTER: Coutelle O 

PROVIDER: S-EPMC4453651 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature