Effects of Transforming Growth Factor-β1 and Basic Fibroblast Growth Factor on Proliferation of Cell Cultures Derived from Human Vestibular Nerve Schwannoma.

The influence of transforming growth factor-β1 (TGF-β1) and basic fibroblast growth factor (bFGF) on growth of cell cultures derived from unilateral vestibular nerve schwannomas was investigated. Cell cultures were initiated from 9 schwannomas and characterized immunocytochemically with antibodies against S-100 and type IV collagen. The effects of TGF-β1 and bFGF on DNA synthesis in chemically defined serum-free medium were assessed by measuring the incorporation of 5-bromo-2′-deoxy-uridine (BRDU) into cellular DNA. Cell proliferation was evaluated with an electronic cell counter. Reverse transcription polymerase chain reaction (RT-PCR) was performed using oligonucleotide primers specific for TGF-β1 and TGF-β2. TGF-β1 stimulated DNA synthesis in a dose dependent manner. Maximal stimulation was observed at a concentration of 1 ng/ml, which induced a nearly 2-fold increase in DNA content. This effect was not seen when TGF-β1 was added in the presence of neutralizing antibodies. In addition, antibodies against TGF-β1 significantly reduced DNA synthesis in control cultures without supplemented exogenous growth factors. bFGF alone had no significant effects on DNA synthesis. In contrast, when TGF-β1 and bFGF were added together, the mitogenic response was much greater than produced by TGF-β1 alone. RT-PCR showed that the cultured cells expressed mRNA for both TGF-β1 and TGF-β2. We hypothesize that TGF-β1 is an autocrine growth factor for human vestibular nerve schwannomas in culture. A similar mechanism might be involved in the growth of these tumors in situ. [ABSTRACT FROM AUTHOR]