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

Author： Weerda Heiko G. Gamberger Tobias I. Siegner Axel Gjuric Mislav Tamm Ernst R.

Publisher： Informa Healthcare

ISSN： 0001-6489

Source： Acta Oto-Laryngologica, Vol.118, Iss.3, 1998-07, pp. : 337-343

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Abstract

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.