PDGF-LIKE GROWTH-FACTOR FROM SV40-TRANSFORMED SMOOTH-MUSCLE CELLS PROMOTES GROWTH IN AN AUTOCRINE OR PARACRINE MANNER

We investigated the growth characteristics of smooth muscle cells tran sformed by ori-defective simian virus 40 plasmid DNA (TSMCs). TSMCs de monstrated a significantly higher proliferative activity when compared with nontransformed smooth muscle cells (SMCs). The SMCs were not abl e to proliferate in media with 5% plasma-derived serum (PDS) instead o f fetal bovine serum, while TSMCs grew under this condition. When the DNA synthesis of quiescent SMCs was reinitiated by the addition of ser um or platelet-derived growth factor (PDGF), the amount of [H-3]thymid ine incorporation into DNA varied with the concentrations of serum or PDGF and decreased on type V collagen compared with the other collagen substrates. In contrast, the TSMCs showed no differences in the amoun t of [H-3]thymidine incorporation into DNA among the various concentra tions of serum or PDGF and different types of collagen. When quiescent SMCs were cocultured with TSMCs, they showed a remarkable increase in the amount of [H-3]thymidine incorporation into DNA, which was most i ntensively inhibited by type V collagen. These results suggest that TS MCs can promote the growth of TSMCs and SMCs in either an autocrine or paracrine manner and that they proliferate independently of the colla gen matrices. Trapidil, a pyrimidine derivative that may inhibit the a ction of PDGF, decreased the number and cAMC levels of TSMCs in the me dia with 5% PDS in a concentration-dependent manner. The addition of p olyclonal anti-PDGF-B antibody induced up to 59.5% inhibition of enhan cement of DNA synthesis of SMCs cocultured with TSMCs. The level of cy clic adenosine monophosphate (cAMP) increased in the TSMCs compared wi th the SMCs. There was, however, no difference in the cAMP levels of e ither cells between the various types of collagen. Thus, the release o f PDGF-like growth factor and an accumulation of cellular cAMP may be related to an increased DNA synthesis of TSMCs. (C) 1994 Academic Pres s, Inc.