Effects of transforming growth factor-beta 1 on collagen synthesis, integrin expression, adhesion and invasion of glioma cells.

Transforming growth factor-beta 1 (TGF-beta 1) as a potent modulator of cell-extracellular matrix (ECM) interactions may be related to poorly understood ECM-associated features of glioblastomas, such as diffuse brain invasion, rarity of extracranial metastasis and marked ECM production in vitro. We therefore studied TGF-beta 1 expression in glioblastoma biopsy specimens and cell lines by using reverse transcription-polymerase chain reaction (RT-PCR). The cell lines were also examined by Western blotting and immunocytochemistry. To determine effects of TGF-beta 1, glioma cell lines U-138MG and U-373MG were incubated for 48 hours with TGF-beta 1 (0.1, 1, 10 ng/ml) or with antisense phosphorothioate-oligodeoxynucleotides (APO) designed to specifically inhibit TGF-beta 1 gene expression. Thereafter, collagen synthesis was determined by isotopic labeling with 3H-proline; integrin expression by flow cytometry; adhesion on collagen types I and IV, laminin and fibronectin by adhesion assays; and invasion through reconstituted basement membrane by invasion assays. We found that TGF-beta 1 was expressed by all glioma cell lines at protein and mRNA levels. Pretreatment with TGF-beta 1 increased the amount of collagen synthesis/cell, upregulated the alpha 5 integrin chain of U-138MG cells, and facilitated adhesion on all ECM substrates, while invasion of U-138MG cells, but not that of U-373MG cells, was markedly reduced. Conversely, pretreatment with APO reduced TGF-beta 1 protein expression levels, inhibited adhesion and increased invasion of U-138MG cells, but did not affect collagen synthesis. We conclude that exogenously applied TGF-beta 1 exerts marked effects on ECM-related features of glioma cells.(ABSTRACT TRUNCATED AT 250 WORDS)