Relationship between cell migration and cell cycle during the initiation of epithelial to fibroblastoid transition.

The NBT-II rat bladder carcinoma cell line, which displays epithelial to mesenchymal transition or EMT in response to FGF-1 stimulation, was used to study the interrelationships between cell cycle and cell scattering and locomotion. Time-lapse video microscopy experiments were performed with asynchronous growing cells and lovastatin-arrested cells. FGF-1 stimulation induced cell movement in cells in all phases of the cell cycle, except G2 + M phase, in which cells did not respond to stimulation. The delay between cell stimulation and cell movement depended on the age of the cell at the beginning of cell stimulation: cells less than 4 h old when stimulated by FGF-1 had a 1-h delay whereas cells more than 4 h old had a 3-h delay. Cells stimulated before they were 4 h old were temporarily arrested in their cell cycle progression. Older cells underwent mitosis on schedule. Lovastatin-treated cells were shown to be synchronized in the G1 phase and to migrate simultaneously after FGF-1 stimulation. These results indicate that the G1 phase was a critical phase for FGF-1 induced cell migration during epithelial to fibroblastoid transition. Copyright 1999 Wiley-Liss, Inc.