Glioblastoma angiogenesis and tumor cell invasiveness are differentially regulated by ?8 integrin.

ABSTRACT: Glioblastoma multiforme (GBM) is a highly invasive brain tumor that develops florid microvascular proliferation and hemorrhage. However, mechanisms that favor invasion versus angiogenesis in this setting remain largely uncharacterized. Here, we show that integrin ?8 is an essential regulator of both GBM-induced angiogenesis and tumor cell invasiveness. Highly angiogenic and poorly invasive tumors expressed low levels of ?8 integrin, whereas highly invasive tumors with limited neovascularization expressed high levels of ?8 integrin. Manipulating ?8 integrin protein levels altered the angiogenic and invasive growth properties of GBMs, in part, reflected by a diminished activation of latent TGF?s, which are extracellular matrix protein ligands for ?8 integrin. Taken together, these results establish a role for ?8 integrin in differential control of angiogenesis versus tumor cell invasion in GBM. Our findings suggest that inhibiting ?8 integrin or TGF? signaling may diminish tumor cell invasiveness during malignant progression and following antivascular therapies.

SUBMITTER: Tchaicha JH 

PROVIDER: S-EPMC3193578 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature