Microtubule-targeting agents in angiogenesis: Where do we stand?

Mechanisms involved in the anti-angiogenic effects of MTDs. Scheme representing the mechanisms involved in tumor angiogenesis (top) as well as those involved in the anti-angiogenic activity of MTDs (bottom). Once the angiogenic switch is turned on in tumors, the secretion of pro-angiogenic factors increases, leading to the activation of neighbouring endothelial cells. This activation results in endothelial cell proliferation and migration, basement membrane (BM) and extracellular matrix (ECM) degradation, and finally capillary tube formation. Bone-marrow-derived circulating endothelial progenitor cells (CEPs) are also involved in tumor angiogenesis. The anti-angiogenic effects of MTDs can be schematically classified in direct effects when they act on endothelial cells and indirect effects when they act on tumor cells. The effect on TSP1 can be viewed as a mixed effect as it is both mediated by endothelial and cancer cells. These cellular effects all result in anti-angiogenesis through the inhibition of endothelial cell migration, proliferation and differentiation as well as ECM and BM degradation. The impairment of CEPs mobilization and viability is also involved, but through mechanisms which remain to be determined.