Transforming growth factor-beta 1 stimulates contraction of human glioblastoma cell-mediated collagen lattice through enhanced alpha 2 integrin expression

Rapid invasiveness is a feature of the highly malignant glioblastoma tumor and is closely related to patient prognosis. The interaction between extrac ellular matrix (ECM) and cell surface receptors such as integrin heterodime rs play a key role in the process of tumor invasion. We investigated the ef fects of transforming growth factor-beta (TGF-beta 1), which is a mitogenic factor for glial cells. on integrin expression in T98G human glioblastoma cells using an in vitro model 3-dimensional collagen lattice. Exogenously a pplied TGF-beta 1 dose-dependently enhanced collagen lattice contraction. A mong the inhibitory antibodies tested against alpha integrin subunits, the anti-alpha 2 antibody, P1-E6, alone prevented the enhanced contractile resp onse by TGF-beta 1, whereas any alpha integrin antibody (including P1-E6) h ad little effect on lattice contraction when cultured without TGF-beta 1. R T-PCR analysis revealed that TGF-beta 1 strongly increased alpha 2, integri n transcript level. Furthermore, pretreatment with antisense phosphorothioa te oligodeoxynucleotides against human alpha 2 integrin using hemagglutinat ing virus of Japan (HVJ) liposome-mediated transfer prevented the effects o f TGF-beta 1 and also reduced the lattice contraction even in the absence o f TGF-beta 1. This data indicates that increased expression of alpha 2 inte grin is responsive to enhanced collagen lattice contraction by TGF-beta 1. We suggest that TGF-beta 1 exerts its effects on the invasive property of g lioblastoma cells via upregulation of the alpha 2 integrin subunit expressi on.