Inductions of fibroblast-like morphology and high growth activity by low-dose CPT-11 in PC12 cells: role of tenascin

The chemotherapeutic agent CPT-11 induces apoptotic cell death in various c ells. In the present study we examined the effect of CPT-11 in rat pheochro mocytoma PC12 cells. When PC12 cells were treated with CPT-11, two distinct reactions were encountered. A high dose of CPT-11 induced apoptotic cell d eath mediated by caspase cascade, whereas a low dose of CPT-11 induced irre versible cell morphological changes. The cell shape of the transformed PC12 cells was similar to fibroblasts, and these were termed FLTP12 (fibroblast -like transformed PC12). FLTP12 cells showed some differences from the orig inal PC12 cells. In addition, cultured media of passed FLTP12 cells induced same cell transformation in PC12 cells. To examine how this transformation may be triggered, the possible involvement of a growth factor(s) mas inves tigated. Among those tested, the possible involvement of basic fibroblast g rowth factor (basic-FGF) was observed, whereas basic FGF antibody did not a ffect the induction of cell transformation. Molecular sieve analysis reveal ed that transformation-inducing factor is large molecule protein Like cell attachment factors(> 100K), and we demonstrated the direct involvement of t enascin in the transformation of PC12 cell. (C) 2000 Elsevier Science Ltd A ll rights reserved.