EFFECTS OF TRANSFORMING GROWTH-FACTOR-BETA-1 AND BASIC FIBROBLAST GROWTH-FACTOR ON PROLIFERATION OF CELL-CULTURES DERIVED FROM HUMAN VESTIBULAR NERVE SCHWANNOMA

The influence of transforming growth factor-beta 1 (TGF-beta 1) and ba sic fibroblast growth factor (bFGF) on growth of cell cultures derived from unilateral vestibular nerve schwannomas was investigated. Cell c ultures were initiated from 9 schwannomas and characterized immunocyto chemically with antibodies against S-100 and type IV collagen. The eff ects of TGF-beta 1 and bFGF on DNA synthesis in chemically defined ser um-free medium were assessed by measuring the incorporation of 5-bromo -2'-deoxy-uridine (BRDU) into cellular DNA. Cell proliferation was eva luated with an electronic cell counter. Reverse transcription polymera se chain reaction (RT-PCR) was performed using oligonucleotide primers specific for TGF-beta 1 and TGF-beta 2. TGF-beta 1 stimulated DNA syn thesis 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-beta 1 was added in th e presence of neutralizing antibodies. In addition, antibodies against TGF-beta 1 significantly reduced DNA synthesis in control cultures wi thout supplemented exogenous growth factors, bFGF alone had no signifi cant effects on DNA synthesis. In contrast, when TGF-beta 1 and bFGF w ere added together, the mitogenic response was much greater than produ ced by TGF-beta 1 alone. RT-PCR showed that the cultured cells express ed mRNA for both TGF-beta 1 and TGF-beta 2. We hypothesize that TGF-be ta 1 is an autocrine growth factor for human vestibular nerve schwanno mas in culture. A similar mechanism might be involved in the growth of these tumors in situ.