FIGURE 2.

Revascularization following AATs. Tumor endothelial cells (ECs) have different phenotypic characteristics from normal ECs. Anti-angiogenesis therapies (AATs) fully or partially regressed the vessel in the tumor. Non-functional empty basement membrane sleeves were found in fully regressed vessels, while EC degeneracy was shown in partially regressed persistent vessels. Although fully regressing the vessel in the tumor might inhibit the reuse of ECs, severe adverse effect and toxicity on the cardiovascular system are not negligible. Moreover, AATs trigger the ECs to release various exosomes with enriched proangiogenic molecules such as VEGF. Increases in proangiogenic exosomes and EC proliferation following AATs stoppage support the subsequent revascularization including new angiogenic sprouting, intussusceptive remodeling, vessel co-option and mimics, and thus promoting the tumor progression and metastasis. Future studies need to identify more key exosomal cargos as well as elucidate the mechanisms by which proangiogenic exosomes are released and how they contribute to the revascularization.