Glioblastoma angiogenesis and tumor cell invasiveness are differentially regulated by β8 integrin
Menée sur des lignées cellulaires, des tumeurs humaines et à l'aide de xénogreffes, cette étude identifie le rôle joué par l'intégrine β8 pour réguler, de façon différentielle, l'angiogenèse et le processus invasif dans le glioblastome multiforme
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 β8 is an essential regulator of both GBM-induced angiogenesis and tumor cell invasiveness. Highly angiogenic and poorly invasive tumors expressed low levels of β8 integrin whereas highly invasive tumors with limited neovascularization expressed high levels of β8 integrin. Manipulating β8 integrin protein levels altered the angiogenic and invasive growth properties of GBMs, in part reflected by a diminished activation of latent transforming growth factor β (TGFβ), which are extracellular matrix (ECM) protein ligands for β8 integrin. Taken together, these results establish a role for β8 integrin in differential control of angiogenesis versus invasion in GBM. Our findings suggest that inhibiting β8 integrin or TGFβ signaling may diminish tumor cell invasiveness during malignant progression and following anti-vascular therapies.