Effects of transforming growth factor-beta1 and basic fibroblast growth factor on proliferation of cell cultures derived from human vestibular nerve schwannoma.
The influence of transforming growth factor-beta1 (TGF-beta1) 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-beta1 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-beta1 and TGF-beta2. TGF-beta1 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-beta1 was added in the presence of neutralizing antibodies. In addition, antibodies against TGF-beta1 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-beta1 and bFGF were added together, the mitogenic response was much greater than produced by TGF-beta1 alone. RT-PCR showed that the cultured cells expressed mRNA for both TGF-beta1 and TGF-beta2. We hypothesize that TGF-beta1 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.
Weerda
H G
HG
Department of Anatomy, University of Erlangen-Nürnberg, Erlangen, Germany.
Gamberger
T I
TI
Siegner
A
A
Gjuric
M
M
Tamm
E R
ER
D000328:Adult; D000368:Aged; D018929:Cell Culture Techniques; D002455:Cell Division; D004247:DNA / Q000096:biosynthesis*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology* / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D008934:Mitogens; D009464:Neuroma, Acoustic / Q000473:pathology*; D010865:Pilot Projects; D016133:Polymerase Chain Reaction; D012583:Schwann Cells / Q000166:cytology / Q000187:drug effects*; D016212:Transforming Growth Factor beta / Q000494:pharmacology* / Q000502:physiology
D008934:Mitogens; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; D004247:DNA