Limited role for transforming growth factor-β pathway activation-mediated escape from VEGF inhibition in murine glioma models.

ABSTRACT:

Background

The vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-β pathways regulate key biological features of glioblastoma. Here we explore whether the TGF-β pathway, which promotes angiogenesis, invasiveness, and immunosuppression, acts as an escape pathway from VEGF inhibition.

Methods

The role of the TGF-β pathway in escape from VEGF inhibition was assessed in vitro and in vivo and by gene expression profiling in syngeneic mouse glioma models.

Results

We found that TGF-β is an upstream regulator of VEGF, whereas VEGF pathway activity does not alter the TGF-β pathway in vitro. In vivo, single-agent activity was observed for the VEGF antibody B20-4.1.1 in 3 and for the TGF-β receptor 1 antagonist LY2157299 in 2 of 4 models. Reduction of

SUBMITTER: Mangani D 

PROVIDER: S-EPMC6693192 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature