Issues

Cytotoxic agents in use for treatment of cancer may also display antiangiogenic effects, but the underlying mechanism is poorly understood. At equitoxic concentrations that do not inhibit cell proliferation, microtubule-targeting agents docetaxel, epothilone B and vinblastine, clearly abrogate human umbilical vein endothelial cell migration, invasion and organization to tubelike structures. In contrast, endothelial cell motility upon treatment with cisplatin or doxorubicin ressembles that of untreated cells. Microtubule-targeting agents affect the integrity of the tubulin and the actin cytoskeleton. Live image fluorescence microscopy shows that less F-actin stress fibers (in red) are formed and F-actin rings appear around the nucleus (in blue). The arrows point towards the direction of supposed cell movement. The disorganization of the actin cytoskeleton is associated with early inhibition of Rac1 and Cdc42 activity, being Rho GTPases that tightly coordinate cell motility. For details, see Bijman et al. in this issue.