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 cells. In the present study we examined the effect of CPT-11 in rat pheochromocytoma PC12 cells. When PC12 cells were treated with CPT-11, two distinct reactions were encountered. A high dose of CPT-11 induced apoptotic cell death mediated by caspase cascade, whereas a low dose of CPT-11 induced irreversible 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 original 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) was investigated. Among those tested, the possible involvement of basic fibroblast growth factor (basic-FGF) was observed, whereas basic FGF antibody did not affect the induction of cell transformation. Molecular sieve analysis revealed that transformation-inducing factor is large molecule protein like cell attachment factors (>100K), and we demonstrated the direct involvement of tenascin in the transformation of PC12 cell.